More seriously - because of a combination of not having socialized medicine (so we have to pay for our own drugs) and because the US doesn't do nationwide bargaining with drug companies (and therefore gets much worse deals). In the end this looks like US customers paying higher prices, subsidizing pharma research which everyone else then takes advantage of.
What we gain from this is the entire point of what we're supposed to get from patent law enforcement in general. Patents, and their enforcement, incentivize companies to spend lots of money to innovate.
If the patent law wasn't enforced for Ozempic et al, then people would get these drugs for cheap. But that would also mean that companies like Novo Nordisk would not be incentivized to spend money developing the next generation of drugs. That's the tradeoff we make with patents: for 20 years, the company gets a monopoly and gets their huge profits, incentivizing them to spend money on R&D. After 20 years the patent expires and everyone gets their drugs for cheap.
Why is the optimal amount 20 years and not 10 years and not 15 years and not 30 years? A good solution is to have the length of a pharma patent depend on how much further investment the company does in new research after a drug comes to market, so for example if drug X cost $100 million to bring to market then the government gives a patent of 10 years with a 1 year extension for every $10 million the patent owner can demonstate it has done on further new research up to a maximum of 20 years.
This way pharma companies are directly incentivized to put money into research rather than the current method which I suspect is less efficient overall.
I don't claim that 20 years is optimal rather than 15 or 25. The optimal length of time for patents is very hard to estimate, as any experiments one would do with that number would have to be conducted over extremely long timescales, timescales long enough that the actual effect of innovation, and thus the relevance of those experimental results, would change over the course of the experiment.
Changing the length of patents based on how much money companies spend on research might sound like a good idea, but it's actually a bad idea because it creates bad incentives.
Currently, patent law rewards inventions with compensation (monopoly on using the invention) proportional to how useful the invention is, not how much effort is spent creating the invention. If company A spends $1 developing an invention that generates $10/year of sales, and company B spends $10 developing an invention that generates $1/year of sales, then company A gets effectively reimbursed more by the patent system (although both companies make their money back with a 20 year patent timeline). The patent system gives rewards proportional to the value if the invention, not proportional to the amount of money spent inventing. Therefore, companies are incentivized to produce the most useful inventions, not directly incentivized to spend the most money on inventing. That's good because that's the end result: at the end of the day, we want useful inventions (we all get them for free after 20 years!); we don't directly want money spent on inventing because that's just a means to an end.
If the patent system rewarded spending money on R&D by indirectly reimbursing that money as you proposed, that would shift the incentives away from inventing useful things to incentivizing spending more money. That would be bad: really what we want is for useful things to be invented, so we should design a patent that incentivizes that above all else. Under your system we would probably see a lot more money being poured into useless dead end projects that will never work because the companies have less incentive to be stingy with their R&D money and less incentive to maximize the potential impact of their inventions. We would see fewer useful inventions per dollar spent on R&D.
If we didn't have patent law, it's not the case that we would all get Ozempic for cheap. Instead, we wouldn't get Ozempic at all! Because no one would have ever spent the money to develop it in the first place.
The patronage of politicians who are in the pocket of pharma corps, I would assume?
Like, 'why does the government not oppose these oligarchs' is a question that affects every domain of policy and politics, and it generally has about the same answer in every case.
Every time someone criticizes the wealthy and their control of teh system, someone jumps in the comments to say 'yeah but communism is worse so we shouldn't do anything about it'.
You are the only person here talking about communism, and it's entirely irrelevant to the conversation.
The voters only have two realistic parties to choose from, thanks to the mess that is first-past-the-post voting and the way it enforces a two party system.
If both parties are sucking up to oligarchs, the voters have no way to express their anti-oligarch sentiments through voting.
Of course there are. There's polling, for example. That does matter to politicians and their campaign staff. Is there evidence that very many voters care about the issue at all?
I've found that a higher dose of Zepbound once every two weeks works pretty well. I'm sure the brightest minds at drug companies are working on a way to make this impossible as we speak.
Right now 7.5mg when I was doing 5mg. I think I'll go up to 10mg the next time I talk to my doctor. I don't have any rationale except that once a week felt like it was hitting me pretty strong (nausea, I had some bouts with diarrhea that may have been related/exacerbated by the zepbound), and since the price is the same, why not just drag it out until I start to feel hungry again?
I also feel like there might be something to the idea that when trying to lose weight putting your body (or at least my body) on a bit of a rollercoaster is better than letting it adjust to a steady state. In the past, I've had success switching to carb-loading when I plateaued trying to lose weight.
Also it's nice to have a day or two to remember how good food can taste and how much I enjoy it.
Would love to have some mild aversion to food. I’m a few months in and wondering if the drugs actually work. About to take 10 mg because not a single symptom or side effect so far. Still eating everything in sight. Grr.
I know we're both joking, but I think if Trump voids foreign pharma patents, that gives the EU the right to ignore US patents, and the US gets the worse end of that deal.
Not exactly. They bargain with the pharma companies, and the pharma companies sell them at very low prices. Partly this is because an entire country has a lot of bargaining power, partly it's because they know these countries are poor and can't afford to pay US prices, and partly it's because the pharma companies know that the countries always have the nuclear option of refusing the deal and infringing the patent so they don't want to play hardball. But the agreements are legal, the patents are being respected, and if they had legal permission to ignore the patents they would pay much less.
If the manufacturing cost is really in the $5 dose range, and if Bam-15 proves out (https://pmc.ncbi.nlm.nih.gov/articles/PMC7224297/) the companies better make every dollar they can before the market crashes under them. That seems consistent with what they are doing.
According to an Advisory Board report, the same patented drug from Novo Nordisk is $169/month in Japan, not exactly a poor country and $83/month in France (which is also not poor). Clearly the US is being fleeced - I'd honestly rather we paid Novo Nordisk the Japan or France price than we pay compounding pharmacies who didn't develop anything. Of course, that would take the government negotiating drug prices for us.
Novo Nordisk is Danish, and the shortage of ozempic in Europe at the start was because it sold for so much more in America, as well as the much bigger market, that it made economic sense for the company to go "Yippee!" and export everything produced to the US rather than sell it at home. They've since ramped up production to cover all the demand, but the free-riding was going the other way, as it were: because they can charge more in the US, that was where it made sense to sell the drugs.
This sounds like a win-win to me. If Trump wants to actually improve the economy (rather than just repeat Elon Musk's lies about the economy) he should do it. I'm sure "tariffs" will resolve any reciprocity concerns.
I think given the costs involved in pharmaceutical innovation, the reduction in incentives that this should cause would be a disaster even if pre-existing bad policies mean that the loss of profits would not be as large as it would be if Europe was like the United States when it came to medical prices.
Tanking? A 6.8% drop in the dow over this last month? Not wonderful, but show me _one_ photo of a stockbroker splashed at the bottom of a skyscraper for me to take it seriously.
edit: A current photo, not 1939, and not photoshopped, AI generated, or otherwise synthetic.
It's probably a major loss for the US companies that produce the drugs and sell then in the EU. The EU has a population of 450 million to the US's population of 330 million per Wikipedia, so that more than doubles their market. And if the profit of producing and patenting new medications is cut in half, then there's less of an incentive to produce those medications. Not great.
The EU does have more people then the US, but American pay way, way higher prices for drugs then Europeans do. Looking it up, ~50% of world Pharmaceutical sales are in the US (as opposed to ~25% in Europe).
Based on recent experience I wouldn't expect Trump to be constrained by existing legsl approaches or internal coherence. He'll declare via executive order that gila monsters are US citizens so the patent alteady belongs to the USA, or it's being taken as reparations for Danish fentanyl, or something. And dare everyone to do anything about it
But both American and European consumers win big, even if the pharma industry loses. Patents are in practise mostly a scam to transfer wealth from ordinary people to big corporations.
How much would Ozempic etc cost per month if there were no patents, and a free market?
Lilly has rolled out a program of Zepbound vials for $499 a month if you are a cash payer to their direct pharmacy. They are closing in on the compounding pharmacies' price in any case.
I realize you hate the FDA, but as they've already decided the emergency is over and you claim it's the pharma companies that will be enforcing this ban, I fail to see how DOGE firing the FDA has any effect except locking in the current status quo and ensuring no future emergencies are declared and no future drugs are approved?
I'm pretty confused as to whether it's the FDA's job or Novo Nordisk's job to go after telehealth startups and pharmacies illegally selling patented medications. My guess is it's a combination of both. Novo Nordisk might be the one who files the lawsuit, but the FDA will probably have to give some regulatory guidance that no, you can't really prescribe 0.51 mg and say you've gotten around the whole issue.
For the record, I think the FDA is acting correctly here.
I'm not sure HOW they should be handled, and something related to the concept is beneficial, but what we've got probably isn't. If nothing else, the "reveal the process" part needs to be made EXTREMELY stronger.
As a person with a number of bogus patents ... the current US system is absurd.
I don't know *HOW* to fix it, but one thing that would be an improvement over what we have is to just limit the number of US patents granted per year. Require the patent office to stack rank the applications and only the top "N".
Google AI says the US granted about 350,000 patents in 2023. Maybe we try limiting the number to 10,000 - 20,000.
Note that this doesn't necessarily fix DRUG patents, but it is probably still an improvement over what we have. We can iterate from there (except not really because the US Congress is pretty bad at iterative law tweaking).
One possibility would be a prize for a treatment that solves a particular problem, much like the British Admiralty did with a prize for solving the problem of determining a ship's longitude at sea.
Someone in another comment says that FDA approval and patents are technically two separate things, and compounding pharmacies have technically been violating patents this whole time. So you might think that the disapproval of an FDA that couldn't do any enforcement due to DOGE stuff would be ineffectual.
In practice, though, it probably does matter. If the drug companies had sued compounding pharmacies during the official shortage, news articles would have mentioned that they're suing these companies for doing something the FDA has approved. But now, those articles would say that the compounding pharmacies getting sued are going against FDA regulations, so the optics might be a lot better for the drug companies now. In that sense, the FDA can exert a some pressure without actually doing its own enforcement.
It doesn’t look that way to me, but I’m going to have to admit that I don’t understand exactly what the relationship is supposed to be between FDA approval and intellectual property. In any case, this wouldn’t be “marketing” – it doesn’t face customers at all. It would be more like mutual aid on regulatory and legal enforcement. Whether that’s a good thing or not depends on whether you think it’s good for those things to be enforceable.
Why don't insurance companies cover these weight loss drugs? I would think that the savings from all the obesity-related health conditions would be worth it.
(A quick google search shows a variety of conflicting answers.)
Many of these conditions don't cause problems until old age, and patients go off private insurance and onto Medicare at 65. So it's not worth it for insurance companies to spend money now to prevent a patient from having a heart attack at 70.
It might be worth the *government*'s time, but first of all, they checked and it isn't, and second of all, there's an awkward issue where from a purely economic perspective, the government wants you to drop dead ASAP, because seniors don't pay tax but do cost money in Medicare costs, so it's not always (from a purely economic perspective) worth their time to make you healthy.
I've thought about that in relation to smoking/social security before. I hate smoking, but I wasn't as mad at smokers after I learned that their early deaths make up for all their extra health costs. I guess I wasn't sure how many of the obesity-related costs show up before age 65.
It also seems that health insurance companies do care to a certain extent about some of these things--I'm nagged about once a month via email by my employer-based health insurance about their program to keep people from developing diabetes and I really want to email back saying "Leave me alone, I'm a skinny guy who runs a lot." But I guess that program is cheaper than brand-new drugs.
Huh interesting. I know that things like the British National Health Service spend more on preventative public health measures like anti smoking or obesity campaigns. On the basis it saves them money long run. Wonder why their economics are different. Maybe to do with owning the hospitals directly?
Well, it's entirely possible that one of the two governments simply did their numbers wrong, either re: the efficacy of the campaigns or the saved costs.
They have done the economic analysis in the UK and smoking saves the NHS money net because they die sooner. The govt. pushes anti-smoking to avoid sickness and premature death.
Is it just that they die sooner, and/or the billions raised in tax meaning they more than pay for their own treatment in aggregate? The last time I looked into it, the govt was a few billion £ up on net from smokers. Hence implementing a tax on vaping - not because vapers appear to cost anything (so far), but they're missing the billions in 'profit' they enjoyed from smokers.
The UK is a classic “single payor system” plus reimbursement is a consequence of approval that uses Health Economics to determine “value for money”. The net result is that many drugs remain unapproved in the UK (essentially rationing. See Leqembi for Alzheimer’s Disease) as an example.
The NHS bears the cost of preventive treatment and the benefit of lower future healthcare costs. In the US, people change insurance companies frequently enough that some other insurance company is likely to receive that benefit, not your current insurer.
This is interesting. I think in Germany there's a system in place to make sure this doesn't happen, so that people don't get cheap private insurance while they're young then go back to public when the conditions start coming in.
Not sure how the German system works with low/no income though
People are usually auto-enrolled into public insurance and switching is generally only allowed in specific circumstances.
I don't know all the details but my impression is that you either have to be self-employed or making a bunch of money to be permitted to switch to private. Then you're generally not permitted to switch back, though there are exceptions.
The result is that the low / no income folk generally have public insurance because they don't qualify for private.
That is quite correct. Additionally less than 10 percent of the people in Germany have private insurance, as it is only allowed if you earn more than 70.000€/a.
It is when your other desiderata include things like "nobody gets preventative health care without paying for it" and "severance of a commercial relationship with a private health care provider also severs all responsibility for future health outcomes of their past standard of care".
Healthcare isn't health. But if we think broadly, there policies that can affect deaths from traffic accidents, homicides etc which cause the US in particular to have high morality rates.
"FDA regulations say that during a shortage, it’s legal for compounding pharmacies to provide medications without getting the patent-holders’ permission."
That's not correct. The regulations say you don't need the FDA's permission. The compounding pharmacies are still (probably) infringing the patents and are liable for that. I don't know why the patent holders have not sued, but my best guess is it would be bad publicity to sue someone for providing medicine when you yourself cannot provide enough of it.
Can you explain the difference between "don't need FDA's permission" and "legal" in this case? Why is the FDA going after patent-infringers for reasons other than patent-infringement?
Apparently, patent law and the FDA regulation of drug manufacture are separate considerations.
Perplexity says:
Section 503A of the Food, Drug, and Cosmetic Act allows compounding pharmacies to create medications that are "essentially copies" of commercially available drugs only if those drugs are listed on the FDA's drug shortage list. In such cases, the FDA does not consider the drug to be "commercially available," thereby permitting compounding under certain conditions, such as not doing so "regularly or in inordinate amounts". However, this does not exempt compounders from potential patent infringement claims under the Patent Act, as the FDA's permission to compound during shortages does not override intellectual property laws.
From what I remember from the Covid times, the FDA actually does more. When a producer builds a production sites for drugs, then the FDA checks that the procedures of producing the drug are safe, and that industry standards at this site are met. For a new high-tech medication like the Covid vaccines, I think this included visiting the site, checking that industry standards are met, and that the production protocols and the procedure for detecting production errors make sense and minimize the risk of contamination. This process is needed for every new production site, even if the company already has a few approved ones for the same drug. Though obviously the first site will be scrutinized a lot more.
I imagine that for drugs that are easy to mix with standard procedures, this is probably only paperwork. I guess the company needs to promise that it's not just a filthy kitchen, but that they meet common production standards. Like having someone who mops the floor once a week, and not producing two different drugs on the same table at the same time.
I don't really know, but it would make sense to me that "don't need FDA's permission" means that you are allowed to skip exactly this process.
All this is completely orthogonal to patents. One question is whether the produced drug meets the necessary quality standards. The other is whether the company is allowed to produce and sell the drug. Perhaps the FDA also check patents as part of the general approval process, but it's not the whole process, and probably only a small part (if it's a part at all).
The compounding pharmacies making “bootleg” ozempic aren’t regulated by the FDA, they’re regulated by state pharmacy boards. Drug manufacturing facilities for pharma, on the other hand, are FDA regulated and inspected.
This. When I'm really sick, I don't eat because I don't want to and eating makes me nauseous. I easily can lose several kilos that way.
Then I get better, and I eat again, and whaddya know, those missing kilos come flying home! And my appetite hasn't reset so that I am now adjusted to eating less.
If there was some way to squash carb cravings, I'd have much less problems losing weight. Yes, I do eat salads, no I don't like mayonnaise, but what I need (or what my body tells me I need) with that is a bread roll, or two slices of bread, or something like that.
If I could give up eating toast or sandwiches, I'd lose weight, and I know this because I did lose weight when strictly restricting my daily carb intake. So why can't I just do that again? I don't know. Lazy, greedy, no willpower, stupid? Sure, fine, but that doesn't tell me *why* I want to eat a loaf of bread and not, say, a pound of steak or a whole chicken.
Yes, exactly—same as we tell alcoholics to drink less. Works famously, yeah?
I read the linked piece from Scott’s response, and it reminded me of a different book from around the same time, The Obesity Code. He mentions that telling fat people to eat less only addresses the proximal cause—just like telling an alcoholic to drink less.
The big question that some people refuse to acknowledge is: Why do some people have so much trouble eating less?
The recently chubby will explain it’s because of willpower or depression or tasty food. The chronically overweight know that there’s something else at work for themselves.
I was raising my eyebrows over people saying "just eat more salad" but now since I do this myself (and way more veggies and less carbs) I have to admit the are true. And it doesn't feel hard anymore. So it's more like good habits bad Habits. And it helps a lot for our whole life to find the good ones and get rid of the bad ones.
I once worked with a porker who dutifully ate salad each lunchtime at his office desk. But he lavished so much mayo on it, a third of a bottle each time, that the calories from that more than offset what he imagined he was saving by munching on rabbit food.
Unfortunately, this seems to work for some phenotypes and not for others. My body seems to get a good difference between eating something truly filling and a bowl of shredded paper (or a fresh salad). So, after eating a lot of salad, I get unbearable cravings for high-calorie things. I keep better shape on a high-fat diet.
That doesn't change the fact that ingesting less calories DOES work.
And if you actually take the time to discuss the issue with chronically overweight people, a hell of a lot of them won't even acknowledge that simple fact.
In the end any solution must address this base problem one way or the other. But if people aren't willing to acknowledge this as being the issue in the first place, they can't really find any solution to that problem.
"Why am I ingesting too many calories?" might have many answers. But agreeing that "too many" even is a thing is the relevant start of the search for a solution.
Reducing the problem to "eating" is already part of the issue for many. Many drinks also have a lot of calories.
That's right. CICO isn't the end of the conversation, but it is the basis for the conversation. If you don't believe in the truth of CICO, you have no way to identify effective interventions.
You can calculate that pretty easily. Your basal metabolic rate can be calculated from your gender, height and mass. Add any kind of exercise/body movement to the equation and you know how many calories you are approximately burning.
This is warning that I will ban comments like these in the future. They're facile, suggest ignorance of an extremely long debate about exactly how this works scientifically and how to think about it philosophically, and are just going to make lots of people really mad. See https://slatestarcodex.com/2017/04/25/book-review-the-hungry-brain/ for a tiny part of the relevant debate.
This comment, while being non-chalant, simply states an objective truth. It's simply the first law of thermo-dynamics restated for an organism.
Accepting this base truth is really important; since any solution must address the problem. Why a person is ingesting too many calories must be figured out to devise a workable solution. But when not acknowledging that this is the base issue people can easily get distracted by supposed miracle cures.
There are many people out there who genuinely state that they don't know why they are obese as they are only eating "healthy" food. The mere fact that the amount of calories dictate weigth, regardless of whether a specific source of calories is considered healthy food, is truly ignored by many actual people.
So in the end, while each person might need a different approach, from a biological and physical standpoint it doesn't matter how you reduce your calorie intake: change of diet, change of habits, taking a 1000$/month drug ... unless the outcome of that reduction is to ingest less calories than you burn, you won't lose weigth! The importance of this statement can't be overstated IMO. That you, of all people, find this scientific base truth so offensive that you threaten to ban people stating it, is really concerning to me.
ANY argument on how to address a weight problem must in the end always address this core truth. There is now way around it. And any proposed solution can always very easily be quality checked by evaluating whether it's achieving this very simple goal.
Trying to supress this core truth is not conductive to solving the obesity epidemic.
*Your* comment is fine, his isn't. I think the difference is the time and effort you put into writing a post that engages the issues in some depth, while his didn't.
A helpful metaphor I heard - if you're such a fan of the first law of thermodynamics, why even worry about calories? You can just think in terms of *mass*. Presumably drinking lots of water will increase your weight, and drinking less will decrease it. There, problem solved!
The reason this isn't true is that the body regulates its weight very closely. If you drink a gallon of water (=8 lbs), you won't permanently gain 8 pounds. You'll just pee it out over the next few hours.
In the same way, a healthy person who eats too many calories will just lose the calories somehow. Some of this will be feeling full until they eat fewer calories later, some of it will be increased drive to exercise, some of this will be increased metabolism, and some of it will be weird things most people don't even think about (apparently your body can vary its caloric burn rate by ~400 calories daily just by fidgeting more or less, in a way that the average person wouldn't notice).
An obese person who tries to eat fewer calories than their bodily regulation system wants will then gain those calories back somehow, either by being so hungry that they give in and eat later, or by feeling more urge to exercise, or by metabolizing or fidgeting less. These effects are natural-seeming enough and powerful enough that "just ignore the drives using willpower" is about as effective as "just use willpower to hold the water in and never pee it out".
(this isn't 100% true; in healthy people the regulatory system usually has some slack, and with enough slack you can actually do quite a lot with willpower - but by the time we're talking about GLP-1 drugs we're probably talking about people for whom the regulatory systems are pretty broken).
This is why there are so many drugs that can make people gain weight (eg antipsychotics) or make them lose weight (eg GLP-1s). It's why people report so much variability in dieting (the same diet, followed when I was 25 vs. 35, had very different effects on my weight!) Understanding these systems is table stakes for talking about nutrition at all, and one reason that nutrition conversations on the Internet are so dumb is that they're constantly interrupted by people who are proudly ignorant of them and interject "But thermodynamics!" when other people try to hold useful conversations.
>An obese person who tries to eat fewer calories than their bodily regulation system wants will then gain those calories back somehow, either by being so hungry that they give in and eat later,
This completely dodges the premise. The person who gives in and eats could, in the alternative, not give in and eat. I can absolutely, 100% guarantee you that someone who eats 50 calories a day (to include essential nutrients) will lose weight over the course of 6 months. Do you deny that it is physically possible for a person with agency to construct a scenario whereby they eat 50 calories a day for 6 months? Is devising a device that prevents someone from driving to the grocery store or ordering food online really in the same universe of physically impossible feats as “holding in your pee forever”?
Somewhat related, but the only diet that has worked for me is not Keto, but Chinese Keto. Imagine Chinese food with no rice. It wasn't just that I was happier eating the food because I liked it, but there seemed to be some biological effect making me feel more satisfied and full when I ate Chinese Keto specifically. I'm guessing this somehow came downstream of what I ate growing up - maybe the kind of enzymes my body was already used to producing? Not sure, but I would've never figured that out if I just stayed on the CICO train.
No, you can't just think in terms of mass, as you own metaphore demonstrates. Drinking lots of water will increase your weight in the same way as picking up a dumbbell will. Your body can't store water and water is energetically neutral to your body. It can't build a single cell from you drinking water. What drinking lots of water will do instead is that you deplete your body of minerals. And resorbing water from your intestins and removing it from your body through your kidneys and urine actually consumes energy. So at best drinking lots and lots of water will actually make you loose weight in the long run (in a very very unhealthy way). Which you just admit yourself in the second paragraph. So why did you make this absurd point in the first place?
"In the same way, a healthy person who eats too many calories will just lose the calories somehow."
Sorry, but no, this is just plain wrong. A healthy person will absorb every single calorie it can. The amount of calories required for the body to function will be consumed right away, and every other calorie will be stored. Which is just a fancy way of saying that the body will turn it into cells. And those cells will be fat cells. You can turn those into muscle cells, if you exercise a lot. Which is why muscular people also have a high BMI without actually being obese.
Your body doesn't have many options for getting rid of excess energy. There is only three in total.
Option 1: not absorbing the calories in the first place. This is actually an illness and pretty dangerous for the people affected, if it is permanent.
Option 2: increasing the body temperature. This also isn't a real option. If it increases the body temperature by much, we call this fever. And if we increase it too much, you simply die.
Option 3: muscle movement. Unless you are execising, the only way for your body to move muscles is to shiver. I don't know of many healthy people who shiver without being cold. But you are the medical professional here. So maybe you know something I don't.
So no, your statement is just plain wrong.
All the ways you continue to describe on how healthy people get rid of excess calories don't fit the discussion. Because you are essentially claiming that excercise will deal with it. At which point those calories are no longer excess calories. They are actually required by the body to perform the excercise. A healthy person who is eating MORE calories than required to perform all body functions will inevitably gain weight. That's what the first law of thermodynamics demands.
"An obese person who tries to eat fewer calories than their bodily regulation system wants will then gain those calories back somehow, either by being so hungry that they give in and eat later,"
Which is exactly what the OP stated. You can't gain weight without actually ingesting those calories. What you are trying to claim here is that those calories don't count because "something something". But that's besides the point. Yes, life isn't fair. And some people have a harder time not ingesting more calories than they need than others. But that doesn't change the fact that the problem is those calories being ingested. And that you need to find ways not to ingest them.
Which is why drugs which diminish your appetite even work in the first place. If it wasn't about those calories, those drugs would do nothing.
And by obscuring those facts on purpose, you are simply spreading misconceptions.
In this comment threat alone I read that some contraceptive made a person gain weight. How many calories exactly does this pill have?
I read people claiming that a high calorie diet would make them lose weight. What they actually meant is that a high fat diet was better at saciating them than a high card diet. Which is actually helpful to know. Getting rid of those french fries actually is a lot more helpful than getting rid of the steak. Especially if combined with lots of fiebers; read fiber rich vegetables like salads, cucumber, tomatos, etc.
"one reason that nutrition conversations on the Internet are so dumb is that they're constantly interrupted by people who are proudly ignorant of them and interject "But thermodynamics!" when other people try to hold useful conversations. "
IMO the exact opposite is true. People willfully ignoring that fact leads to a miriade of misconceptions which leave people helpless and essentially force them to buy a 1000$/month drug. Because apparently that's the only possible solution (which it surely is for some people). When in fact many people actually have alternative options.
The core issue is that people have a misconception about how nutrition works. 7000kcal ingested in excess to what the body needs essentially translates into 1kg/2lbs of body weight gained. Which mean that if you eat half a cheese sandwhich per day in excess of what your body needs, you will end up at 300+lbs within only 10 years. Little things matter!
And so does the truth. Which you are obscurring here on purpose. Nothing a wrote is news to you.
>An obese person who tries to eat fewer calories than their bodily regulation system wants will then gain those calories back somehow, either by being so hungry that they give in and eat later,
That's calories in, calories out! Giving in and eating later is the thing we want to avoid, because CICO!
>or by feeling more urge to exercise,
[Pretty sure you meant "less urge"]
That's calories in, calories out! Not exercising, even though you should, is the thing we want to avoid, because CICO!
Whether we avoid those things through willpower (works for some, not for others) or fantastically expensive drugs (works for almost everyone if they can afford it), or things like bootcamps and subscription diet services where the "willpower" is external, we're avoiding them because taking in fewer calories than you expend causes weight loss.
>An obese person who tries to eat fewer calories than their bodily regulation system wants will then gain those calories back somehow, either by being so hungry that they give in and eat later, or by feeling more urge to exercise
With the drugs that cause weight gain, how does this typically work? Do people eat more calories? Does it lower their metabolism? Do they become more lethargic?
I read through the article and the lipostatic baseline article tracks with my experience; if I gain a few pounds I mentally feel fat pretty much immediately and quite quickly shred it from portion control. I've maintained within the same +/- 5 pound range for the past few years without much effort, despite highly variable levels of exercise. This includes a month on the potato only diet that was mentioned here a few years ago; I thought it was quite good but then I had a family trip where I could no longer maintain it, culminating in a large ice cream that my potato gullet was not ready for.
However, I don't see how that doesn't square with CICO. It very much is a willpower thing; I weigh myself, see that I have gained weight, feel bad about it, and actively reduce my calorie intake to get rid of it. I also quite obviously employ willpower to firmly avoid high calorie junk like soda (NEVER) and candy (NEVER); I have a drawer full of candy that I get for holidays office functions etc. that I just awkwardly hold on to because I refuse to eat it. Conversely, if my weight goes down a bit I'll fine eating a bit more and will gain a little bit back to normal.
Is that not calorie in calorie out? I do maintain my lipostatic baseline per your book review, but I fundamentally do so by experiencing the qualia of body weight in proportion to my lipostatic baseline (which self reinforces due to my own conscious bodyweight expectations) and manipulating my calories in/out accordingly.
My experience is that the main objection to CICO or more generally "diet & exercise" is that it isn't a question of mere willpower, but that some people have naturally high weight set points and if you eat fewer calories than will keep you at that point, you would be unbearably hungry. But in this post, you mention this study:
"In 1965, some scientists locked people in a room where they could only eat nutrient sludge dispensed from a machine. Even though the volunteers had no idea how many calories the nutrient sludge was, they ate exactly enough to maintain their normal weight, proving the existence of a “sixth sense” for food caloric content. Next, they locked morbidly obese people in the same room. They ended up eating only tiny amounts of the nutrient sludge, one or two hundred calories a day, without feeling any hunger. This proved that their bodies “wanted” to lose the excess weight and preferred to simply live off stored fat once removed from the overly-rewarding food environment. After six months on the sludge, a man who weighed 400 lbs at the start of the experiment was down to 200, without consciously trying to reduce his weight."
This suggests that one of the following must be true:
(1) Anyone can lose weight without feeling unbearably hungry just by restricting the *types* of foods they eat.
(2) While this works for the nutrient sludge, this doesn't work if you loosen your restrictions to foods like potatoes and chicken. You really have to eat nutrient sludge, and this is an unreasonable diet to expect of people.
(3) Even the availability of non-sludge-like foods causes this diet to fail: having the ability to go to the grocery store and buy delicious calorie-dense food would make you unbearably hungry in a way you wouldn't be if you're forced to eat the sludge.
(4) The study is false, and the people were really unbearably hungry.
I'm unsure of which one you believe. I get that just citing CICO elides a bunch of important details, but this study really seems to support the CICO/willpower view and I haven't seen a great reason why that's not the case.
CICO and willpower isn't the same thing though. I don't think that being obese is the result of a moral failure of the person affected. But it still is caused by consuming more calories than required to maintain a healthy weight. Thus the question becomes what to change to reach a healthy weight, and more importantly, how to maintain it longterm afterwards. Because most people can lose weight, if they really want to. But maintaining it is more difficult.
And honestly: spending 1000$/month for a life time to me seems as ridiculous an option as the nutrient sludge dispenser one.
Well, Bob, for the first 25 years of my life I was someone who naturally stayed slim. I did make some very minor efforts to avoid gaining weight — like not eating desserts, and not keeping cookies in the house — but I wasn’t perfectly consistent even with those very mild restrictions. It didn’t matter. My weight always stayed in the same slim-but-not-thin 10 pound range. Then I began taking birth control pills, and my weight went up 20 pounds in 2 years. It took me a while to suspect that the bc pills were the culprit, and before realizing the pills had caused the weight gain I tried quite hard to eat fewer calories and exercise more. I had the same experience most people do: It turned out to be surprisingly hard to stick with this plan. I’d stick with it consistently for a while, using a LOT of willpower to do it, and lose 5 lbs. Then over the next couple weeks I’d gain it back.
Then I stopped the bc pills, and over a summer lost all 20 extra pounds with no effort at all. I did not follow a diet or count calories. I just wasn’t very hungry. I then returned to staying in my previous slim range with no planning and no serious effort.
I now understand better people who are overweight and can’t lose the weight. I think many of them have bodies that, like mine, tend to have a stable weight — except their stable weight is high, while mine was moderate to low. So stretch your mind a bit, Bob, and try on the possibility that the reason you maintain a normal weight is that you are lucky, not that you have more common sense of willpower than overweight people. Then maybe you won’t be so inclined to say sneery shit when people talk about having trouble losing weight.
This is going too far in the other direction, and is also just as snarky in an equal and opposite manner. As someone who managed 15kg of sustained weight loss by examining the various factors that went into my weight gain and reversing them, just like you did, I think that a purely defeatist "there's nothing to be done" attitude isn't any more helpful than a blindly optimistic one.
You may have examined the factors, but I did not. I had one real factor, the bc pills, and I can't even remember how I came to the idea that they might be the cause of the weight gain.
But before I figured out that I should try stopping the bc pills I did think of some of my habits (which were the same ones I'd had when I easily stayed slim) as factors. lI did not exercise systematically. (On the other hand, I got around entirely on foot and by bike, in a place where home, work and stores were not particularly near each other.). I did sometimes buy a muffin with my coffee. I liked to put honey in my yogurt and my tea. I sometimes pan fried things that could have been baked. These habits I thought of as the factors that had caused my weight gain.
And when I tried to lose the 20 lbs while still on the BC pills I did make a big effort to change all those things. But it was terribly hard to stick to. And, like most people, I have done some hard things that have taken sustained effort. I wrote a dissertation. I adopted a child as a single woman and homeschooled her while holding a job. I have done backpacking trips in the sierras, carrying my tent and food and water on my back, walking uphill all day long on the first day, as we ascended. . But nope, I could not lose those 20 lbs while taking bc pills.
Not eating as much as your body is asking you to is hard in a different way. It's not a matter of simply putting up with some periods of hunger. There is a constant undertow towards food that goes on, even when you are not feeling hungry. Your body thinks it needs more food, even if you think it does not, and it exerts pressure in all kinds of ways, just as it does when you short yourself on sleep. It becomes vigilant for food cues. It plagues you with food images. It attacks in the middle of the night when you get up to pee, suddenly insisting that you can't bear not having a bowl of cereal.
I am sure there are people who truly are lazy and self-indulgent, or unable to analyze factors and make an effective plan, but there are plenty of people who are stuck with being overweight who very obviously are able to identify factors, plan, and follow a hard plan. *Scott* struggles with overweight! I am sick of people who think that if they can be slim, everyone else can, or even, like you, that if you can lose weight, they can. They are not you. If they could have, they would have.
There is only one line of snark in my answer to Bob -- the first line -- and I think he richly deserved it.
I'm not sure what you mean when you say you didn't examine the factors, and then say that the pills were the major factor for you. That sounds to me like you found the major factor behind your weight gain!
For me I quit my stressful job, moved back from the US to Australia, and began walking everywhere again. None of these took effort to maintain: it was all upfront costs in the form of changing my environment. This made me drop about 5kg without even thinking about it. I then calorie counted my way through another 15kg drop because I was bored during COVID, regained 5kg over about a year, and stabilised just below the top of the healthy BMI range.
I understand that starving yourself is difficult. I did it out of boredom because I was in the middle of lockdown and it was still hard. I just...don't think it's impossible, or totally ineffective for 100% of the population. What I found was that eating at a deficit taught me how to optimise my food intake so that it was the most satiating for the least calories, which is something really valuable that I still use today.
Seeing people be so dismissive of an approach that worked for me feels like it could turn others off approaching weight loss by trying different things. It feels like learned helplessness. I know that I can't grab everyone by the hand and show them the 1995 satiety index, or the studies on fibre and gastric emptying, or that blog post about liver energy use and dietary protein, but I can at least say "hey, learning stuff about weight gain and loss sometimes works, no guarantees of success but also none of failure."
The problem isn't that people eating to many calories would be lazy or self-indulgent. The problem is that they are ingesting too many calories. Any kind of moralization doesn't help with the issues. Figuring out WHY they ingest too many calories does.
In your case you figured out that this pill changed your perceived hunger in a way that made it exceedingly hard to maintain the weight you wanted to maintain. But you understanding that you were ingesting to many calories was still important. It just took you a while to figure out why this changed for you, when you had no such issues before taking that pill.
Other people have other circumstances. But the main factor remains: the amount of calories must somehow be brought down. Whether this is through intermittent fasting, a change of diet, the use of one of the three substances the article above mentioned, pure will power or any other means doesn't really matter.
There is no silver bullet to solve everything. But understanding that the calorie intake must change, and then devising a solution on how to do that, is what's leading to a solution. Your BC pill was entirely elective, so you were able to just change that. Other medication has similar effects, but isn't elective. On such scenarios one can blame the medication, but that won't solve the issue. Finding alternative solution to reduce calorie intake does.
That's why trying to suppress this core issue is so hurtfull to the conversation. As is blaming obesity on some moral failure of the individual. But the solution to the later isn't the former.
i’m fairly overweight and am slow to lose weight so i have to make a lot of effort to even maintain my current weight, but lifestyle (barring other medical issues) is obviously the only way to sustainably lose weight. nothing is wrong with me and i’m fairly active and eat well, people just have different metabolisms and have to live accordingly. i think being realistic about it (without wallowing in pity or blaming yourself) is the only solution—only you can make yourself healthy, not any miracle drug.
more and more research is showing that glp-1 agonists definitely cause temporary vision changes & might be linked to increased risk of blindness (it had been known to worsen diabetic retinopathy this is a potential link to NAION in otherwise healthy individuals.) blindness in severe diabetics would be an ok trade off—it just worsens the symptoms while controlling everything else—but not in obese but otherwise healthy individuals.
the free market and a loose regulatory approach has in fact failed by making an expensive “miracle drug” whose risks are not completely understood & produces patients reliant upon them for life so widely available.
Yeah, I know about that. But are you aware of the stats for improved odds regarding many
bad illnesses and systemic conditions people on these weight loss drugs have? Some are downstream of weight loss, some seem to be direct effects of the drug. I’ll bet the reduction in HbA1C (a blood sugar measure) alone on these drugs way offsets the risk of blindness from glp1 agonists. Google “H1C As predictor vision loss” and you will find many recent studies. Here is one: https://bmcophthalmol.biomedcentral.com/articles/10.1186/s12886-022-02608-3
Seems to me you have an attachment to the idea that dieting is the only safe approach to the problem of overweight, and have seized on these findings about vision problems in, so far, a scattering of patients. And you’ve failed to consider other info, which is very well known, that must be considered when evaluating risk/benefit ratio of these drugs.
This actually does not work, because of the large variance in how much nutrition different people with different digestive systems get from the same food with the same number of calories listed on the box.
Of course, you could update your claim to 'digest less nutrients than you burn', but then the obvious reply is that we have no way to reliably measure either of those things on an individual basis, so it's impossible to follow that advice in a practical manner.
>Of course, you could update your claim to 'digest less nutrients than you burn', but then the obvious reply is that we have no way to reliably measure either of those things on an individual basis, so it's impossible to follow that advice in a practical manner.
As long as your body obeys the laws of thermodynamics and can't create calories out of nothing, you can always reduce your intake until you start losing weight. As for following that advice in practice: use a scale.
How would you feel if I told you "whip yourself bloody every 30minutes, every day, for 6 months or even multiple years"?
That's what you're saying. That's what "just eat less" is. You're telling people to torture themselves constantly so that at some point in the distant future, they'll maybe look a little bit better.
No, I'm not saying that. I've been replying to user "darwin" and his claim that it's literally impossible to count calories because of variance in digestion. If your personal digestion is that much different from what's printed on the food packaging, then maybe take responsibility for the variance in your body because who else can? Find your personal conversion factor, apply it, and keep updating it. Do some basic science if it helps, write shit down: how much you exercise, how many calories you consume (purely as per the packaging), how your weight changes in response. Nobody is asking that you get the caloric balance right down to single digits or every single day without fail because that would be insane to even try. Just realize that weight control is a marathon. Look honestly at what you're doing in the long run and what effect it has in the long run.
Just because you're groping half-blindly towards the goal doesn't mean you can't reach it. Just don't close your eyes entirely, which I know is tempting when everyone keeps telling you how hard it is for this or that reason.
How seriously do you expect anyone to take a comparison of "reduce your intake of food in a controlled manner" and "whip yourself bloody every half hour"?
It actually is useful, because it means that a) not consuming calories results in weight loss and b) the body has a certain rate of consumption of calories at all times.
From that you can conclude that there is some amount of calories (potentially a range) that equals the consumption of calories of your body, at which point you will neither gain or lose weight, and if you consume less than that amount, you will lose weight.
You would be surprised how often I have to have this discussion just to disentangle this most basic mechanic of weight loss from the very different and more complicated problem of how to sustain that weight loss. If you do disentangle these two things, it might let you focus more on the latter.
It doesn't just work in theory. It also is scientifically proven to work in practise. Whether you switch to a diet that keeps you saciated for longer, or whether you skip meals consistently, doesn't really matter.
See for example: "Intermittent fasting and health outcomes: an umbrella review of systematic reviews and meta-analyses of randomised controlled trials"
"Actually, I've figured out a diet that actually works: Take in less calories than you burn."
I'm trying to provide a helpful response so please take it that way.
For many/most overweight people, your "Take in less calories than you burn" is equivalent to "Inure yourself to being hungry all the time."
If you find the second formulation to be helpful then I would suggest using it rather than the first. The second has the virtue of acknowledging why the first is empirically so difficult.
If you find the second formulation to not be helpful then maybe don't offer the first?
Yes! That's the whole thing. If you pace your meals so you don't ever think, "oh, it's 7pm already, I guess I'll go eat", but instead think, "oh, I'm quite hungry, I am looking forward to dinner at 7pm", then you will lose weight. And it has to be stomach hunger, not head hunger. Your goal is to learn not to silence this sensation with a snack, but to revel in it, the way people enjoy the heat and cold of a sauna or muscle soreness after a good workout: "oh, I feel properly hungry, this means I am eating the right number of calories and will enjoy my next meal".
In my experience even as a naturally slim person, you don't have control over whether you feel hungry. You may THINK "oh I already ate a lot, I shouldn't be feeling hungry again so early" or vice versa, but the body often has other ideas, and it will get increasingly insistent the longer you try to ignore it.
> and it will get increasingly insistent the longer you try to ignore it
That actually doesn't track with the experience of people trying that. Wether it's "Alone", "7vsWild" or other experiments where people try to survive in the wilderness for an extensive period of time, all of them unanimously report that the feeling of hunger goes away after 2-3 days and only resurfaces in waves.
That's actually what you'd expect to happen, because otherwise our ancestors wouldn't have been able to successfully hunt once they went into a caloric deficit for a day or two ...
I didn't say you have control over you feeling hungry. The point is to recognize the sensation and reinterpret it. If you get off a stressful conference call and go buy a snack bar to calm down, that's not real hunger, you have to recognize it and stop yourself: "I am not hungry, I am angry".
And you do the same with real pangs of hunger: "I am hungry, this means my diet is working, this means I am transforming my body into the body I want, every minute I successfully resist these pangs until the next meal brings me closer to the result I want, not feeling hungry so close to the next meal actually means I've overeaten".
And you do the same when eating: "I've eaten as much food as I need, the only reason I want more is because satiation hasn't kicked in, instead of reaching for more I should wait until it does".
Intermittent fasting works very well for me. I eat at most 8h a day; meaning I don't eat anything for 16 hours a day. Yes, sometimes, rarely, I still get hungry late in the morning. Waiting one to three hours for lunch isn't that much of a challenge though. It mostly only happens when I skipped dinner as well anyways.
I've been doing it for almost three decades now. It works very well for me. Whenever I'm on vacation and don't do it due to me always having breakfest with the family, I start to gain weight. So I'm not magically thin.
If that was true, the article above wouldn't exist. The drugs described clearly managed to make the people taking them "take in less calories than they burned". That's how they lost weight.
If you actually want to lose weight the obvious follow up question would be "How?".
Then the next step would be to investigate all sources of calories consumed and to determine whether an adjustment there would be feasible and helpful. If it is, fine.
If it's not, the next question would be if an adjustment in life style would help. Can you limit accessibility to snacks? Can you do some kind of fasting like intermittent fasting? Can you reduce consumption of heavily processed foods and takeout? Can you eat more slowly with frequent pauses to give your body time to process and report?
If that didn't help the next step would be to investigate your medication (if you are using any) for stuff that's known to mess with the metabolic feedback loops. And, if you happen to take any, to research wether substitutes are available.
If that's not the case the next step would be to look into possibilities in increase exercise. This usually doesn't result in weight loss. But it transforms fat cells into muscle cells, which many people tend to prefer.
If that doesn't work either, investigating the viability of the drugs mentioned in the article above is an option. If you can afford them and they help, fine.
If you can't, or if they don't, then more drastic measures are required ... or you just give up.
500kcal/day is actually a way to lose weight that's pretty successful in studies. You need those 500kcal/day to get enough proteine, which you can't really dispensed of during your diet.
But it's actually been studied that very low calorie diets tend to be more successful due to immediate and drastic effects, then healthier slower attempts at weightloss with only a slight caloric deficit. However, maintaining the weight afterwards is another story. You still need to adjust the life style to maintain that weight afterwards.
I kinda made the "Bob" method work for like 8 years. It was a little more complex than that though.
First step was a crash diet. 800 calories a day, ironically achieved through the use of fast food. I bought a single meal in that range, kept zero food in the house, doordash didn't exist then, and my roommate was under orders to take my keys if I tried to leave to get food. I did this for about 10 months. Lost 90 lbs. Ganked my gallbladder in the process and had to have it out. Turns out if it doesn't despense bile often enough, you get gallstones and hyperbilirubinemia.
Then step 2, after losing so much weight, exercise was wayyyyyy easier. Unimaginably so. I could run for 5 miles which felt being Goku, considering the rest of my sedentary life. Shin splints and ankle pains when running gone, fewer stitches in the side, and obviously more endurance, because less mass. I started eating like normal again, but exercise mostly kept the weight in check. I'd see-saw about 10lbs within a year, so high volatility and by no means thin, but I was not fat. (Side note: People really are so much friendlier to peiple with healthy weight)
Covid finally ended my spree, not being able to hit the gym, I gained weight, then got depressed which cause me to gain more weight. I'm still 30lbs down off my high water mark, but it's bad reversio . Overall, though I consider it qualified success. Even if I never lose back again, I probably extended my life by going for nearly a decade with healthy bp, triglycerides, etc.
I can't recommend my approach ultimately because there were lots of gastroenteric issues that cropped up because of it. Also, gotta be careful by adding vitamins. Crash dieting is correctly seen as unhealthy. I do wonder though, if this is something that GLP folks can take advantage of, coasting down to a "cruising weight" in the meds, then switching tactics to wean off the meds and eat normally while using aggressive cardio training. Bring the meds back when Covid 28 hits or whatever interrupter might happen that fractures the cycle. It might not work for everyone, but I suspect due to my experience, there's probably a significant amount of folks that don't have to take the ketracel-white forever.
Does anyone know how the ~$200 a month from compounding pharmacies compare to the raw materials? Is it sort of the price we'd expect from a generic version of the drugs? Without knowing anything at all about the manufacturing process, that seems like a high number to me if patents aren't coming into play.
I agree. Several people have claimed that the raw materials could be produced for pennies, though I don't know for sure that this is true. I think that everyone is buying from the same couple of factories that have some level of safety certification (although not as much as the real Novo Nordisk brand or any other normal drug does) and there aren't enough of those to drive down costs. But I agree this is mysterious, and it wouldn't surprise me if the people saying the raw materials are cheaper are wrong.
I know secondhand of a couple of people who have gone this route, and it came out to about $80 US per month at the dosages they were using. I imagine that the majority of that was shipping costs. Make of that what you will
Compounded tirzepatide from a licensed pharmacy is on average about 10x the price of peptides ordered from China. Something like $6/mg compounded vs .60/mg for the peptide. Who knows what the Chinese middlemen are paying but almost certainly a lot less less than .60/mg. So someone on the highest dose would pay like $360/month for the licensed compounding pharm version vs $36/month gray market. (Grey market has some extra expenses for other materials/group testing the peptides so call it $50/month.)
> All of our patients just developed severe needle phobia, sorry, so they need semaglutide gummies.
I think this can be a legit loophole? Needles are scary after all and if it can be administered orally, much much more people will want the drug. Why haven't Novo Nordisk seizes this niche yet.
I think if the patient was previously willing to take the injection (which almost all current GLP-1 patients are), then by definition it's not "medically necessary" for them to have a non-injection formulation.
There's more info at the Recursive Adaptation post. My guess is Novo Nordisk hasn't seized it because they would have to go through a completely new FDA approval process for this "new" drug, it would be very expensive, and there isn't enough real-world demand for it. It's also possible that they tried, it didn't work, and they haven't told anyone because why make life easy for people who are trying to cheat you?
Yeah reading the RA article, conditional on gummies not being a good idea, I put 30% for FDA ban because it isn't "medically necessary", and 70% for it straight up doesn't work.
I wonder about how this relates to EpiPens—there’s a newish nasal inhaler version of epinephrine that the NYT wrote up with a lot of quotes from doctors whose anaphylactic patients were calling from the parking lot of the ER, etc, asking if they “really” needed to inject themselves.
EpiPens are about as medically necessary as medication gets, right? And yet fear of needles really can stop a patient from using the medication, even in a life threatening situation.
At least in some cases, companies avoid releasing new formulations because they're waiting seven years to do so. You see that a lot with sustained-release formulations; 3x daily becomes 2x daily becomes 1x daily, even though they could have easily made the better product from the outset.
Pharma companies would not be successful suing doctors for writing scripts that don’t match their dosing. Maybe in a direct to consumer model of some sort, but when the pharmacy and doctor are financially separated
That aside, any company that charges more than 15% above the g7 average price for a medication should have their patent revoked unceremoniously.
I don't know, if I write a prescription/note saying that it is "medically necessary" for someone to get something, in a way that causes someone else to gain or lose money, I try to always do this in a way that will hold up in court. I don't think case this is that different from when doctors say it's "medically necessary" that someone get a surgery because they're secretly being bribed by the surgeon or something, and then lose their license for fraud.
I also think these telehealth companies are the kind of direct-to-consumer model you're thinking of.
I work in medicine. Lots of regular non tele-health providers use local compounding pharmacies to get patients glp1s. They aren’t attesting to anything being “medically necessary” when they write a script. They are just writing a script for available offered dosing. The onus for filling that drug legally is on the selling entity, the pharmacy. Again if you could prove some sort of illegal kickback scheme then sure, but otherwise you just won’t see this kind of lawsuit imo.
I am claiming that if there is a doctor who consistently writes 0.51 mg scripts, and when the pharmacy calls back and says "can we do 0.5 mg?" says "no, this is medically necessary", and has an employment relationship with a company that profits off of 0.51 mg scripts but not 0.5 mg scripts, and only ever seems GLP-1 patients for this company, then by the 1000th patient like this the regulators will notice a pattern and ask the doctor for documentation that the patient actually needs 0.51 mg, and when that documentation doesn't exist he will get in trouble.
As he puts it: "We need to understand the basic principle here. Patents are a government intervention in the free market, they impose a monopoly in a particular market."
This is from a liberal and relatively mainstream economist, pointing out the obvious weirdness of patents in our modern economy that's supposed to be based on free trade.
"Or maybe I am completely wrong about all of this. I am not an economist and have to take these studies at face value, and anything that touches pharmaceutical companies ends up being corrupted and full of lies. "
Maybe defer to the actual economist who wrote a book on the subject then?
That's not how rational deference to expertise works. No one should defer to one economist when it's clear that the majority of economists disagree with that one (I'm not saying the one economist in this case is a quack, mind you; it's a legitimate minority opinion in the field.)
All well and good – but that's a reason for the state to cover prescription drugs, maybe even overpaying drug companies (they have a greater ability to pay than the average consumer), rather than a reason why individual consumers should pay high prices
I agree that ending medical patents and replacing them with *nothing* might slow medical research in a way that's net bad.
But we could also do something else that is not that. Have the government buy out patents on actually useful new drugs, or have the government and charities set bounties on desired drugs that will enter the public domain once discovered, or have patents that do not grant full monopoly but do enforce royalty payments, or some other better policy that a subject-matter expert could probably think of.
Basically, I agree that we probably need to use money to incentivize research. But if society is going to spend $1B in order to invent a new drug, we can decide where that money comes form and what incentives it creates.
Right now, we are raising that $1B by creating artificial scarcity on important medications. While the pills themselves are cheap and could be made available to everyone who needs them for next to no cost, we instead restrict the supply so that lots of people can't get them at all, in order to create a high price point that pays back the research investment.
This has to be one of the stupidest possible ways of raising that $1B, because it's the only one that involves people *not getting the drug* after it's been invented and made cheap and easy to make. Buying out the patent with $1B in government money might not be the optimal solution, but at least then the government could make massive quantities on teh cheap and distribute it to everyone who wants it at cost.
I just read this and your old post on slatestarcodex. One question I don't see addressed is: what is the value to US consumers from pharmaceutical research being done in US? We pay a lot more for drugs here than the same drugs sold in other countries (acknowledging your point that generics, too, are more expensive than they need to be because of limited competition) -- does the consumer's subsidizing pharma research benefit consumers in the US to a greater extent than foreign consumers who pay less? I think maybe your response would be that if everyone behaved as the Europeans do by regulating/negotiating lower prices, then in the long run we'd have fewer new drugs and more deaths. (Not to put words in your mouth). But isn't it also possible that the savings to consumers that would result from regulation could be funneled to non-privately-conducted research -- and isn't it also the case that a lot of drug research happens at (sometimes) public research universities, so US consumers are actually subsidizing the research directly AND paying more on the basis that they need to cover research costs? And finally, I have read (sorry can't cite a source) that advertising budgets by pharma companies are far higher than research budgets, so isn't the pharma argument that "we pay more to encourage research" just a bit duplicitous?
If I recall right, Richard Posner has argued that the patent system in general is too favorable to inventors (e.g., because first-mover advantage is enough for tech like phones), but he made an exception for pharmaceuticals because the cost of invention is so damn high.
Is Posner assuming that all inventors are also skilled industrialists and salesmen? Because "first-mover advantage" doesn't count for much if you can't move, and you can't move into the market without manufacturing and sales.
Or is the idea that all invention is going to be done as work-for-hire for established industrial corporations?
Then what motivates invention? There's an upfront cost to be paid there and sometimes it's significant. What pays for that other than a temporary property right?
There's different methods. The method Dean Baker advocates for is that the government should offer prize money to anyone who makes an invention, rather than enforcing their monopoly. If that sounds too radical, we could simply decrease the length of time that patents are enforced. Novo Nordisk has had a near-monopoly on legal semiglutides for over 10 years now, and made hundreds of billions from it. Isn't that enough? It's simple enough for amateurs to manufacture in their garage, so all of their profits now are from government enforcing their monopoly.
A large portion of those profits are reinvested into drug discovery. If you reduce those profits you reduce the future availability of new medicines. There's a reasonable debate to be had there over where exactly to put that dial, but it seems a little silly to say that you're fine with patents if they're 5 years but if it's 10 then they're just "government intervention in the free market".
A government prize is just obviously wrong. That substitutes bureaucratic preferences for market incentives. How does that usually turn out?
Market incentives result in prioritizing treatments for chronic conditions that put people on drugs for life over one-time interventions or prevention. In general market incentives are supposed to work because people make more-or-less rational decisions, but health and the things that contribute to it are basically some of the hardest things for people to be rational about because they strongly trigger basic biological instincts.
Being less abstract about it, the US has some of the best healthcare interventions available in the world and spends more on healthcare than almost any other industrialized nation, and yet we're firmly mid when it comes to the actual health of our population. Not coincidentally, we're one of the nations that lets market incentives in healthcare run freest.
> A government prize is just obviously wrong. That substitutes bureaucratic preferences for market incentives.
Why would bureaucrats be the ones setting the prize quantities? There are *already* charitable foundations funding drug development (for e.g. malaria vaccines) on a "prize for success" basis. Making that the main system - replacing patents - could be a relatively simple matter of standardizing procedures, centralizing the 'bounty board' to reduce search costs or other needlessly duplicated effort, and acting as an escrow agency to make sure inventors and buyers both get what they fairly paid for. No need for such a program to have any particular official opinion on which drugs people are allowed to want, at least not beyond excluding uncontroversial egregious abuses like NBC weapons research, money laundering, or making dangerously addictive narcotics even worse.
Market incentives from patents reward rent-seeking, such as development of drugs which delay problems rather than solving them. Clean cure or easy prevention doesn't provide as much ongoing revenue stream. Managing that process creates additional operational overhead, and complex financial risks, which results in a "moat" restricting competition by new firms.
Lump-sum bounties would allow an R&D-specialized firm (even, in principle, some lone genius working out of his garage) to pay investors immediately and in full, hand over open-source plans to production specialists, close the book and move straight on to the next project, instead of being inexorably incentivized to make life harder for desperately ill people who *want to help test* those drugs by burying their best data in corporate counterespionage.
Billion-dollar prizes are going to be a huge political headache, with enormous pressure to cut down on the obvious "waste". They're also going to be much bigger litigation magnets than patents.
The economic models that are used to justify the patent system intellectually don't even model patents as such, rather they are obvious nonsense models that have the result that invention is maximized when the entire social benefit of an invention is internalized by the inventor specifically and therefore "something must be done" to make it possible for inventors to internalize social benefits of their inventions and "patents are something, therefore we must do patents".
The actual case for patents is basically status quo bias. What are the chances that the ideal economic mechanism for promoting invention was discovered by non-economists slightly tweaking a form of cronyistic government prize ("letters patent") used by kings in the mercantile age? Basically zero, yet here we are.
I don't know that it's that crazy to think kings in the mercantile age arrived at an efficient solution to the problem. If those kings went on to defeat other kings with worse solutions, then there would be selection for better solutions.
Will the lowest non-compounded price likely stay around $500 until the patent expires or might it decrease more? I assume if there are new competitors that come to market then it will definitely decrease in price, but if that doesn't happen I'm curious if time will be enough for the price to come down.
If we assume that semaglutide and tirzepatide are perfect substitutes, then my very weak Economics 101 knowledge would suggest that they should compete each other down to the manufacturing cost, which is very cheap.
But in real life that hasn't happened, and it doesn't happen in other similar situations (eg generics with two manufacturers). Maybe a real economist can tell us why.
The basic econ 101 answer is that if there are only a few providers it is easy for them to collude to maintain monopolistic pricing. This “collusion” doesn’t even have to be negotiated; a tacit understanding that slashing prices by one of the providers will lead to retaliation by another is all that is needed. The more providers there are the more likely it is though that a “trade war” will start.
Yes, the search terms are "duopoly" for the special case of two providers and "oligopoly" for the more general case of a few providers. Pricing strategy in a duopoly or oligopoly scenario without explicitly agreed collusion is a form of iterated prisoner's dilemma: each firm can increase revenue in the short term by lowering prices, but if other firms also lower prices by similar amounts (either coincidentally or in retaliation), the total pool of revenue for the market segment goes down and each firm's share of revenue goes down. Any given firm makes more money (in the short term) if they lower prices, regardless of what others do, but everyone makes more money if nobody lowers prices. Optimal strategy depends on how likely other firms are to respond in kind if you lower prices and how likely they are to "defect" on their own.
There are a couple of added wrinkles in most real-world cases. One of the big ones is that production costs usually aren't all the same. If you know your firm can make, sell, and distribute the product substantially more cheaply than your competitors, then you may be able to "win" a price war by ending up in a position where you have a much larger market share, large enough to make up for the price cuts, while your competitor can't cut their own prices further without selling below marginal costs.
There are also sometimes ways to enforce a cartel indirectly by aligning incentives, such as cross-licensing: you agree to license patents to one another and make your products in such a way that each of you is selling something that depends on your competitor's patents. The license fees mean both of you profit any time either of you sells.
David Friedman has a whole chapter about this in his price theory text (Chapter 11 of the linked PDF), plus a few other considerations: threat of new firms entering the market, competition on factors other than price, price discrimination, most-favored customer clauses, etc.
Last month I ordered a tirzepatide pen from them. The brands approved to treat diabetes (Ozempic, Mounjaro) are still sold in multi-use pens that you can portion out. The single-use vials with no preservatives are only for the weight loss brands (Wegovy, Zepbound). I wonder how Novo and Lilly will try to prevent everyone from just ordering the "diabetes" versions to stretch out the dose.
Including shipping and a new customer discount, it was ~$700 for what I will stretch out to 8 doses (so, ~$350/month). The package arrived with no Customs issues, but this was before all the tariff chaos, so who knows what the future holds.
It's the same with pills. For many psych meds my patients take the cost of a high dose pill is very close to the cost of a low dose pill. So I advise the ones who are having trouble paying for their meds to buy the high dose and split the pills if. they're splitable.
I've always thought the reason high dose and low dose pills of a given psych med cost the same is that the amount of drug in a pill is a very small part of what it costs to produce the pill. The other costs, which are the same for high dose and low dose pills, are physically producing and packaging the pills, advertising, development of the drug, etc. Dunno whether that's true, though.
IIRC, during the early days of the opioid explosion, the rationale (according to some sources highly critical of the companies) was more “give them as much of this drug as they need/want/can tolerate for the same price as a lower dose” in order to sell more product. A little counterintuitive in the sense that more product could mean more pills, or more money, but the way they went was just more drug—in fewer pills, if necessary.
Sure, but if we look past that moral question, there's a pragmatic economic consideration that looks like:
Someone getting diagnosed with a condition, getting a prescription for that condition, getting the pills from a pharmacy, and getting all the paperwork and admin associated with that managed, is imposing a real and substantial cost on the system above someone with no condition and no meds.
But someone doing all of that and then getting the 10mg pill imposes almost no costs beyond someone doing all of that and getting the 5mg pill.
So if we want to claim that what people get charged is in some way related to what it costs to treat them, there's no justification for charging much more based on dosage.
>"So if we want to claim that what people get charged is in some way related to what it costs to treat them …"
That's not how pricing is done; people get charged based on the value of the product *to them*, which actually supports the dose-insensitive pricing: the value of a drug to a patient is related to how it improves their life, so they DGAF if it's 5mg or 10mg.
Drug companies do try to do this, by exploiting the classic time/money tradeoff by charging more for time-release or other more convenient formulations, or by selling me-too drugs that are incremental improvements at a higher price than the improvement really justifies.
A lot of businesses do try to. E.g. governments charge taxes proportional to income (or even progressively), cinemas give out senior discounts, and burger places charge €3 to add a piece of bacon to your burger. Price discrimination is ubiquitous.
I don't think I agree with your logic. If a medication I take is highly effective at 10 mg but only slightly improves my symptoms at 5 MG, I'd probably pay more for the higher dose if I had to, assuming that I could budget for it. I imagine other people would, too.
Or, if you need 10 mg to get blood marker x to stay at desired level y, 5 mg might keep your levels at dangerous level z. I'd pay more for 10 mg there if I had to, as well.
You're correct, but you're not disagreeing with my logic. :)
In your example, the 10 mg dose improves your life more than the 5 mg dose, so it's more valuable *to you*.
Someone who responds more strongly to the medication may see the same life improvement from the 5 mg dose as you do the 10 mg dose, and experience unacceptable side effects at the higher dose; they would value the 5 mg dose more than the 10 mg one.
The optimal pricing strategy has to account for the total demand curve; individual demand curves' idiosyncrasies largely cancel out.
There’s a layer beyond (beneath?) compounding pharmacies, which is people buying Semaglutide (et al) from research drug companies, and relying on trusted third-party labs. I haven’t scrolled through all the comments, but how does this ruling affect those outlets?
Can you point to any info on this route? Are you saying that I can pay a seller to mix the peptides for me, and there’s some kind of lab testing and/or reputation to give me confidence what I’m getting is real and safe?
I saw that part - but want to hear more about “trusted third-party labs”. How is trust established? Are there vendors that will mix for me and give me a vial with preservatives? Are there third-party labs that can verify this? I understand why people don’t want to mention specific vendors, but it would be helpful to know how developed this market is and whether there are any best-practices.
Testing by independent labs--you send a sample vial from the lot of ten that you buy. No. Yes.
You gotta read, man. It's not something that can be explained in a comment. The link is there go dive in. It's fairly sketchy. (Not for me personally after reading pretty deeply about it, I stick with compound from a big pharmacy.) If you want mixed for you, trustworthy, regulated, etc. you want compounded, not grey market.
I work at Ognomy Sleep, one of the companies listed on the Lilly Direct page (under Sleep Apnea), and at least in our case, they are partnering directly with telehealth startups with their own independent doctors (so not just pedaling the drug with their “Eli Lilly stooges”). In our case, we do have an objective to diagnose and treat sleep apnea beyond just prescribing tirzepatide, but that is now one of our therapy pathways. Can’t speak for the companies listed under Obesity or connecting with doctors through their other channels, though.
The mechanism doesn't require any collusion, you just only partner with doctors that are okay writing the prescriptions. If your partners stop writing prescriptions, you find different partners.
“For the past three years, ~2 million people have taken complex peptides provided direct-to-consumer by a less-regulated supply chain, with barely a fig leaf of medical oversight, and it went great. There were no more side effects than any other medication.”
I thought this wasn’t true? I had read several articles about a lot of side effects resulting from these compounding pharmacies for GLP1 specifically.
Yes, but what those articles fail to tell you is how many people on regular
drugstore versions of these drugs seek medical attention for gastric side effects, which are very common. And it is not rare for someone on one of these drugs to have such bad nausea or heartburn or constipation they are alarmed or just plain miserable enough to call their doctor or even go to the ER. I do not know whether the brand name drugs cause as many of these side effects as the compounded versions. but neither do the people writing these articles —
at least none that I have seen. Have you seen any that compare complications on brand name to complications on compounded?
I have tried both Ozempic and Mounjaro in compounded formulas. Both gave me brutal constipation and bloating that none of the various remedies/strategies could resolve. If you have GI issues, I would stay away from GLP-1 drugs in any form..
Well, but in the clinical trials 90+ percent of people on the trial drug hung in for the full year. Based on that and other things I’ve read it’s clear that most people find the side effects tolerable. You seem to be in the unlucky 10% who have intolerable side effects. By the way, I read that people on the lowest dose of Mounjaro, which I believe is 5 cc, lost weight about ¾ as fast as those on the high dose, and had far fewer side effects. If you haven’t tried low dose treatment, might be worth a try.
From what I can parse between the lines of the articles: (1) There is a genuine issue in that the compounded versions don't come in single-use vials, so the rate of dosage-related issues is higher. Everything else mentioned in the articles seems to be either (2) a simple recounting of the normal side effects of the medications, or (3) speculation that bad things might happen due to lack of agency-regulated testing. That last bit is presumably what Scott is talking about - despite the lack of agency-regulated testing, there don't seem to have been any reported cases of health problems caused by impurities.
The reason you need to read between the lines is that the drug companies and FDA like to wave their hands around rapidly to try to confuse the reader and/or journalist so they don't distinguish between (1), (2), and (3).
And for what it's worth: While it's clear that (1) is a real issue, it's abundantly clear that many people don't think that the reduced risk from measured vials is worth paying $750 a month for. We ought to consider whether those people may be underestimating or externalizing the risk, but we also ought to consider the possibility that they aren't, and that the tradeoff is worth it.
In general, injecting unclean things is more likely to cause infection than eating poorly prepared things, since your stomach acid does a pretty good job killing most bacteria in the things you eat. This makes (all else being equal) self-compounding and injecting more risky than self-cooking are eating.
FDA site on the subject infuriated me. They give the number
of people on compounded version who seek medical attention due to drug effects, but no data on how many people on the prescription version do so. I doubt that the number of the latter is small. One of the people I know taking the brand name version of the stuff ate a large meal and then spent hours vomiting so violently that she had sore muscles in her sides and back for several days after. Saw her MD, who said, yeah, Ozempic. can do that. FDA site is a lesson in how to obfuscate with statistics.
Yeah, but most meds have some side effects. In clinical trials of these drugs the fraction of subjects on the trial
drug who quit the trial was greater than the fraction of placebo subjects who did, but not unusually high for a drug trial. Can’t remember what it was, but I think somewhere between 5 and 10%.
> But this time if you do anything wrong, or are insufficiently clean, you can give yourself a horrible infection, or inactivate the drug, or accidentally take 100x too much of the drug and end up with negative weight and float up into the sky and be lost forever.
Anxious housewife over the moon at prospect of immortality.
It seems to me that, if you can't recommend buying semaglutide from a Chinese/Indian manufacturer directly. You should instead not-recommend buying retatrutide from a Chinese/Indian manufacturer directly.
The only *real* risk is antibodies -- It seems that semaglutide results in GLP antibodies in ~2% of people over a <I can't remember> months timeline and tirzepatide causes it in <I can't remember>0% over a <similar amount of months> timeline.
retatrutide has no such studies, in my off-the-cuff experimentation local reactions to it seem stronger (bruising, gum swelling) *but* that's an n=1 using something like platelet hitting up an area more to ~= "this will reach your lymphatic nodes and get trained on to produce an antibody that has corss-activity to GLP-1" which is not super sciency.
Given that none of the drugs have good antibody data anyway, and the phase 2 for retatrutide is more than big and good enough to point to it resulting in more weight loss with essentially 0 side effects.
I would suggest people not-recommend that one instead.
There is a drug called retatrutide that is being developed by Eli Lilly as the next-generation version of tirzepatide (Mounjaro). It hits even more target receptors than tirzepatide, and phase 2 trials have shown it to be even more effective at weight loss. Phase 3 trials have not yet been completed, so it is not yet FDA-approved for medical use, and consequently not officially available in the US or Europe.
However, the same Chinese or Indian peptide manufacturers that will sell you semaglutide or tirzepatide will happily sell you retatrutide as well.
The rest of the post discusses the possibility of your body developing antibodies against these drugs, that might potentially cross-react with your own GLP-1. I'm not sure where OP got their data from, they didn't cite any sources, more realistically there is e.g. Mullins et al. (https://pubmed.ncbi.nlm.nih.gov/37700637/) which shows ~2% of tirzepatide-treated patients developing any sort of neutralizing antibody against tirzepatide activity, and <1% of patients developing antibodies that are cross-reactive against endogenous GLP-1.
Anecdotally, OP observes stronger injection-site reactions to retatrutide as compared to the others, and hypothesizes that this might correspond to a higher possibility of such antibodies developing. But they also mention that the link between these two phenomena is weak, which leads them to suggest retatrutide over semaglutide/tirzepatide when ordering from Chinese/Indian peptide suppliers anyway.
For what it’s worth, I’ve been “microdosing” tirzepatide for about 2 months now—1mg/week, not for weight loss but for IBS-like stomach issues that have been so far untreatable.
4 weeks in, all my chronic gut issues resolved. That’s almost 10 years of IBS-D or “bile acid malabsorption” or whatever it was—just vanished over the course of four weeks.
How’d that happen? I can’t wait to read about it. In the mean time, I can’t believe my luck in finding a doctor who suggested trying this.
Hi Jean, this is the same for me. I may be able to help. My long-standing gastrointestinal issues were finally pinpointed as due to an extremely low production of pancreatic enzymes. I started Mounjaro for weight loss and my symptoms completely disappeared. It has been life-changing. Curious, I then found a study which showed that, totally incidentally, Mounjaro increases pancreatic enzyme production by 30% or so.
Since high dose and low dose injection pens cost the same, people are getting prescriptions for high dose pens then breaking them open and using a syringe to get several lower doses out of each. There are lots of how-to videos on YouTube.
He did mention it, unless he edited the article recently?
> So usually they sell all doses at a similar price, opening an arbitrage opportunity: if they sell both 5 mg and 10 mg for $500/month, and you need 5 mg, then buy the 10 mg dose, take half of it at a time, stretch out your monthlong supply for two months, and get an effective cost of $250/month
Oh, yeah, I see that now. Not sure whether it was there all along. I guess the only info my comment adds is that even if you can only get the drug in a pen rather than a vial it's possible to open the pen and draw out part of the drug with a syringe.
You can also "dispense" the auto-injector pen straight into an empty sterile vial (readily available online), and then portion it out with syringes from there.
"Many people have to stay on GLP-1 drugs permanently or risk regaining their lost weight"
Can anyone explain why this is? My understanding is that all these drugs did was curb appetite. Do people just get insane food cravings again or something?
Gary Taubes suggests that „all these drugs do is curb appetite“ is wrong. Instead, they shift fuel partitioning away from fat storage (what low-carb diets also aim to do), which means more energy is available and appetite is reduced. Once a new equilibrium is reached, appetite returns even for people who stay on the drug. See here:
That post just rejects the “set point” mechanism for no real reason (or, the author doesn’t understand it? It doesn’t even seem incompatible with their explanation!)
Parsimony? If I understand this correctly, people would have expected a decision to eat less to result in lower weight, which empirically it doesn‘t, so they arrived at the idea that the brain „defends a set point“, often too high. But why would the brain do that? If Taubes has a different explanation that does no longer need this dubious set-point mechanism then of course he would „reject“ it.
It would be worthwhile looking how pricing works. According to ACT the price of Wegovy in the US is $1000/dose. Here in Switzerland the cost is CHF 188 (US$213 at todays's exchange) - from the same drug companies supplying the US. (source: https://en.comparis.ch/krankenkassen/leistungen/abnehmspritze).
Suspect that’s the gross price ($1000)- the actual price once rebates etc are factored in is likely to be much less (but still considerably greater than in Switzerland).
Thanks. The challenge regarding many of these HE analyses lies with the validity of the assumptions that underpin the calculations. That and the absence of long-term data. Also, generics will be available in the next few years (at least for the first wave).
I’m sure you right about this. I once did CB analysis for large engineering projects and the results had to be perfectly in line with management goals. But that having been said, reductions in cost (say to Swiss levels) will ALWAYS give a better CB ratio. Basically with no downside for anyone.
Of course generics will also help, but at least in this part of the world (Switzerland) generics manufacturers carefully avoid any attempt to seriously disrupt traditional pharma (often they are offshoots of the old firms). And to make things worse we’re going to have to wait several years before the generics are available.
This is strange. I checked the site my pro bodybuilder friends use for the ever varying stacks they try and at $129/5mg of Semaglutide that’s $13 dollars a week (have no idea what bacteriostatic water costs) that’s a BigMac Meal.
Eroids.com is the consumer reports of street peptides - overseas suppliers for any conceivable substance
Another lists $79/5mg or $8 a week. Thats a lot less than $250 I suppose.
One of the things I’ve argued with about the “Big Get Rich” pharma model of trans is that test and estradiol are extremely cheap.
I noticed that Sustanon (mixture of different molecular weight Testosterones) was $55 for 3500mg (10ml) - at every two weeks that’s $550 a year - nobody is making $Billions off a handful of women masculinizing themselves.
Likewise estradiol tablets seem to be $15 for 30 tablets of 2mg, or $100 a year for men feminizing. Lifetime spend of $4000 or so.
It’s amazing how much this has grown since I first looked at it.
>I am not a lawyer but this is all stupid. What are the companies thinking?
I've been listening to the 5-4 podcast on the history of Supreme Court cases, and am coming to realize that 'this is incredibly stupid' is in no way a disqualifying trait for a legal argument to have. If the current judicial regime wants to side with you for political or ideological reasons, they are often willing to approve very stupid arguments to do it (or to ignore your argument and make up their own).
So they may well just be thinking 'throw up as many stupid arguments as possible, which will serve as ablative shielding in the courts as each one takes months or years to be officially legally struck down, and maybe one of them will make it to a sympathetic court that wants us to provide cheap medicine to people and sides with us despite our argument being stupid.'
Worse strategies have won out for major industries in the past.
I've got what probably amounts to a year's supply in the fridge from Hims. Maybe I'll go ahead and try to order from Ro or Henry under the wire to stock up.
But yeah broadly this has been awesome for those of us willing to dip our toes slightly outside the insurance/doctor system. It was fun while it lasted. I lost 50 pounds last year, basically effortlessly, from 220 down to 170. FWIW, I've found that once I'm acclimated to semaglutide, 1/2 or even 1/4 of the prescribed dose can keep me on the straight and narrow. Maybe helpful for anyone else pondering how to stretch their vials in the fridge, as our patent rumspringe comes to an end.
> But this time if you do anything wrong, or are insufficiently clean, you can give yourself a horrible infection, or inactivate the drug, or accidentally take 100x too much of the drug and end up with negative weight and float up into the sky and be lost forever.
Presumably you only get a horrible infection if you inject it, rather than taking it orally? Although I guess inactivation or floating up to the sky are still issues.
I'm not actually in this market; I assume there's some strong reason why most people are injecting when oral administration is usually vastly preferable, but a quick Google suggests only that some people get more side effects. Perhaps I'm missing something
My understanding (nonexpert) is that all GLP-1 drugs require injection except for Rybelsus, a form of oral semaglutide where the manufacturers try to crank up the dose so high that you can get some even though it's got terrible stomach absorption. My understanding is that Rybelsus doesn't work as well for most people and causes more side effects.
In theory there could be a sublingual solution but that's the gummy idea mentioned earlier and so far nobody has gotten it to work.
One of the reasons Rybelsus causes more side effects is because it includes SNAC to "improve bioavailability", which seems to mean punching holes in the stomach or intestinal lining to allow the GLP-1 receptor agonist to get into the bloodstream. (Also, I don't know what happens if one injects a semaglutide+SNAC mixture but I'm not volunteering to try it.)
I know 'America medicine bad' is a stereotype at this point, but just to provide a reference point here in Australia:
- I have a monthly 5-15 min phone call with a doctor (actually a nurse-practitioner) who has been awesome at providing advice and talking through strategies for diet exercise etc.
- I pay A$350 for 5mg including overnight delivery (via a service called Evermed which seems to intermediate with whatever local pharmacy offers the lowest rate). That's about U$220 with current exchange rates.
- When I was on a 2.5mg dose my doctor actively suggested ordering the 5mg vials and dividing up the doses to halve the cost
- That price include *no* government subsidy of any kind - if there's a policy change it can basically only lower the out-of-pocket cost
- The monthly checkin appointments cost A$59 of which I get A$26 back via government Medicare bulk billing rebate
Isn't all this patent skirting just eroding the incentive for pharma companies to develop new drugs? The market system can do a good job either supplying existing drugs or developing new ones but not both. It seems weird to celebrate just shifting on that trade-off. Theoretically the way to do a good job supplying existing drugs and developing new ones would involve non-market systems, which we're making no progress towards.
It hasn't been doing that so far because there's been a shortage and the pharma company literally hasn't had the drug to sell.
Now that the shortage is over, it would do that going forward, which is why the FDA is banning it. I support the ban on that basis, but think there are other things to celebrate about the compounding model. See last paragraph, "It’s no surprise that you can sell drugs cheap if you violate the patent. But it is interesting that the non-cost aspects work out so well. "
Fair enough. I might just be getting triggered by the term "free-market medicine", but I still think experiments in that direction will hit a dead-end.
For context, the cost of bringing a drug to market is ~$1.4Bn USD.
This includes basic research (itself not inexpensive) in a pharmacology lab, putting things in test tubes; checking they work in cells, then whole animals without catastrophic side effects; adequately purifying them (including with regard to chirality, see thalidomide), observation of all regulations during testing in humans (lawyers = £/$) plus the costs of running the drug trials themselves. Scientists and doctors don’t work for free, and neither should they. It all mounts up, financially.
Something like 90% of drugs fail to come to market: sometimes they simply don’t work as expected, or have un-ignorable adverse effects, or your Very Promising Drug is being tested in a few dozen human subjects and one of them dies (drives under a truck / is shot by the police / etc.) in which case everything is halted because to say the death is unrelated to the drug is inductive reasoning. (It might have affected judgement or behaviour, for example.) As most of the money will already have been spent by then, it’s for the successful drugs to recoup the outlay.
See also production costs, financing future drugs and keeping enough cash in reserve in case something bad does get through and a Very Large Number of people require compensation (see Ranitidine etc.). Also profit, of course. Patents, make-what-they-can pricing schemata and a seeming enthusiasm for treat-not-cure strategising do seem inevitable in this light. Compounding pharmacies and generics skip all of this.
Then again, without all of the above, I think it's unlikely we'd have the WHO model list of essential medicines. I’m not sure what practicable alternatives there are.
I have no idea how the cost of bringing a drug to market is broken down and have no industry experience. When I went to look it up, I ran across https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2820562. It looks like most (~80%) of the cost of bringing a drug to market is marketing and sales.
I am left thinking that if the marketing and sales budget of a drug was a mere 100% of the R&D budget instead of 400%, and if GLP-1 agonists followed the same split as everything else, they'd cost $400/month and be very close to competitive with compounding pharmacies.
I may have missed something in the JAMA Network paper. How did you calculate the ~80%?
Marketing and sales: I live in the UK where pharmaceutical companies don't advertise directly to patients, and I'd forgotten this happens in the US. Perhaps this accounts for at least some of the disparity in final cost between the US and elsewhere in the world? I also wonder if the US market is effectively subsidising developing nations.
"When I went to look it up, I ran across .... It looks like most (~80%) of the cost of bringing a drug to market is marketing and sales."
I think you mis-read the paper.
The Key Points at the top says this:
"This economic evaluation study used data from public and proprietary sources to estimate the mean cost of developing a new drug from 2000 to 2018, which was $172.7 million (2018 dollars) but increased to $515.8 million when cost of failures was included and to $879.3 million when both drug development failure and capital costs were included. The ratio of R&D spending to total sales increased from 11.9% to 17.7% from 2008 to 2019."
So the drug companies spend about $900 million (on average) per drug that comes to market. And this is about 20% of the total sales per drug, so the average drug will cost $900 million to bring to market and result in $4.5 billion in sales.
A few years ago when I went on Liraglutide, they gave me a box full of pens and a box of needles. I set the dose myself on the pen.
This year I went on Semaglutide. The different dosages are different products. You get a single pen with 4 doses of a specific size in it. The active compound is diluted s.t. the pen is exactly used up. This comes packaged with exactly 4 needles.
I suppose this prescription technically allows me to buy just needles from the pharmacy as well. After all, one part of the injection process is to test the needle, and if it doesn't work properly it has to be discarded. But they're sure as hell making it as awkward as possible to mess around with dosages.
In general, I grudgingly tolerate price discrimination. But when physical reality makes it hard to do so and the pharma companies try to twist things around to do it anyway, I have zero sympathy.
I also grudgingly tolerate the need to get a prescription before buying a medication. But that mechanism should never be used for economic purposes; it should be purely about safety (and about triage/priorization in extreme cases).
There is also probably some safety advantage in making it hard to administer the wrong dose? Plenty of other injectable products, e.g. epinephrine autoinjectors, are sold in single-use packaging at a variety of doses.
Great idea. Lets totally dump the patent system for pharmaceuticals. It took Novo Nordisk over 30 years and billions of dollars to complete the FDA approval process for semaglutide (liraglutide was the first approximation).
I am sure that without the patent and the extra profits from that, the next pharma looking for the next breakthrough will make that kind of investment out of the goodness of their hearts.</sarc>
The patent system allows the patent holder control all details of the practice of the art. As long as the medicine is patented, compounding pharmacies have no ability to participate in distribution of the pharmaceutical. There is no first sale doctrine in patent law.
> They’re selling their medication in single-dose vials, deliberately without preservatives, so that you need to take the whole dose immediately as soon as you open the vial - the arbitrage won’t work!
Sorry if this is a dumb question, but, can I not still simply freeze the not-yet-used contents of the vial? Is freezing not effective at preserving the medication without the added preservatives?
I'm not an expert on this but I think repeated freeze-thaw cycles are bad for peptides. My guess is that it's fine in real life, but that enough people (including me) would be too nervous about theoretical risks we can't quite disprove to be willing to try.
I think you can get around this. If they give you a vial with enough active ingredient for 4 weeks, use 4 syringes to draw out 1/4 of the solution and freeze the syringes. Each week, unfreeze one and inject it. Then each molecule of peptide was only frozen and thawed once.
(2) "They’re selling their medication in single-dose vials, deliberately without preservatives, so that you need to take the whole dose immediately as soon as you open the vial"
Ha! If people are desperate enough they'll just keep the drugs in the fridge and cross their fingers and risk that taking half the dose now and half the dose later will work out and not kill them.
(3) "There were no more side effects than any other medication. People who wanted to lose weight lost weight."
Well, I hope. I'm currently on the 1g/week dosage and haven't seen any major changes yet. I may have lost a tiny bit of weight, it does seem to be helping my blood sugar, but it's having a weird effect on my appetite - yes, I'm not eating as much at one meal. So hurrah, reduction in intake means reduction in calories means weight loss, right? Except that within 1-2 hours afterwards, I'm hungry again and so I end up eating the same amount, more or less, as before.
Or I'm snacking a lot - constantly grazing. No, now I won't eat a whole bag of crisps in one go - but I eat half a bag, then look for maybe a yoghurt as well, a handful of peanuts, some grapes, half a bar of chocolate, that kind of 'filling in the corners'. It's very odd. Before, I might eat the whole big bag of crisps, but that was enough (at the time). Now, I'm not eating the whole bag, but I'm grazing on several different things at the one time to make up for it.
Which are you on, semaglutide or tirzepatide? A 1mg dose is really small for either. I have done lots better on tirzepatide than I did on semaglutide. I'm at 7.5mg and am 2 pounds away from the blessed 25 BMI, the BMI that shuts medical professionals up when they want to blame your hangnails or hair loss or anything else on being overweight.
Semaglutide. I'm only ramping up because I re-started on the low dosage to get up to the 1g and see how I tolerate that.
The first time I was put on Ozempic and then couldn't get it because of the shortages, my doctor did switch me to Mounjaro (I think) but I couldn't tolerate it and had to come off. So now we're going slow and seeing if everything stays fine and then up to 2g if needed.
But the appetite thing is really weird. I'm getting none of the suppression or lack of cravings alleged, this odd "must constantly snack" all the time instead.
Seems like a good opportunity for someone to manufacture sterilized benzyl alcohol in sealed vials for addition to these unpreserved single-dose Zepbound vials. Hmm...
Does tirzepatide without preservatives *really* go bad immediately once opened? I'm not a doctor or pharmacist but it seems hard to see how the tiny pinhole opening in the vial (which is self-resealing once the needle's been removed) would make the drug become ineffective within a week unless there's a very strong reaction between the fluid and something in air. And there's zero awareness in the general public that the vials can't be opened and split -- I've never heard this mentioned anywhere other than here -- so if deterring people from doing that is the plan, Eli Lilly is doing a terrible job of it. My understanding is that the actual reason people aren't doing this is because until last month, Lilly Direct only sold the 2.5mg and 5mg vials, and only a very small percentage of users are on a dosage below 5mg.
If we’re talking about the versions from Eli Lilly (not compounding pharmacies) the method of injection is a single-use pen, kind of like an EpiPen where you push it down on the thigh and a needle springs out to dispense the dose for you. Unless you pulled the whole apparatus apart and extracted the medication, I’m not sure you could really get half a dose out now and half a dose out later.
When buying tirzepatide from Lilly Direct, Monjuaro is sold with an auto injector pen, Zepbound is sold in vials with standard insulin / subq syringes. I know pharmacies often sell Zep in auto injector pens but that’s not how Lilly Direct does it.
I looked up the patent expiry date for Ozempic, and it seems to be next year. Intuitively this doesn't pass the sniff test, but I could be wrong. Any one know of any information one way or the other?
Most obese individuals could save $200-$300/month just on food costs by using weight loss drugs. Add in savings on gas (MPG), shoe wear, medical visits, and even lower insurance (health/life) premiums—and the real cost is far less than $1,000/month. Plus, a healthier weight could increase income-earning potential. The financial equation might not be as bad as it seems. Thanks for the post!
Studies have found around 6–11% reductions in grocery budget, so unless your hypothetical obese individual is spending $35,000–$40,000 a year per person on food, I don't think you're going to see those kind of savings. Keep in mind the median personal income in the US is just over $40,000, and obese individuals are poorer on average.
I was definitely skewing on the high side and included “food”, which includes eating out. It’s a combination of volume reduction of food, plus food category, ie eating more veggies $5/lb versis meat $10/lb.
and not, are eating a lot of chips, sweetened cereal, cookies etc — you know, junk food carbs. And that stuff is *cheap.*. Switching from that to broccoli and salad makings is definitely going to make food costs go up even if calories are going down
Right. The cost analysis needs to consider reduced food consumption. Someone eating a $15-20 large pizza for dinner might consume only two slices after starting Ozempic - a significant reduction that offsets some medication costs.
The Walmart CEO has noted that GLP-1 users demonstrate lower caloric intake and reduced grocery spending, representing tangible economic savings.
Most importantly, the $1000/month creates an immediate cost framework for obesity that most people need, as we generally struggle to calculate the net present value of future health costs. For those needing to transform their health trajectory, this expense may be a reasonable investment compared to the long-term consequences of remaining obese.
I have long thought that moving away from a patent based incentive model in pharmaceuticals to a generous royalty based system that lasts longer (25 years?) may have advantages. Maybe not for every category of drug, but it is worth considering.
For some added flavor: the direct-to-consumer sales models Novo and Lilly are debuting are very legally dubious. It's illegal for a drug manufacturer to (1) pay healthcare providers to prescribe the manufacturers' drugs; and/or (2) pay patients to use particular healthcare providers. These models may do both, by (1) providing free marketing to providers (by channeling patients to them via the manufacturers' websites) in return for those providers acting as "stooges," as Scott puts it, and writing more prescriptions for the manufacturers' drugs; and (2) steering patients to specifically those stooge providers (again via the websites).
Scott, there is one possible outcome you did not address. Organized crime. These chemicals are much easier and much safer to manufacture than the popular controlled substances distributed on our streets by narcotics traffickers. And the penalties for distributing these weight loss drugs is minimal compared to unlawful distribution of cocaine, meth, and fentynal. Although the weightloss class is not addictive in the traditional sense, those who are on these drugs do become desperate to get them when they are no longer available. Because little expertise is needed to manufacture them and they can be manufactured domestically, I believe organized crime is going to monopolize the industry. This is where the money is, and there is a lot of money to be made by those who can make these products at very little cost, are not regulated, and pay no taxes.
But they do that because recreational drug users actually like taking fentanyl (to the extent that overdoses can cause a surge of buyers to the source that they know to be selling potent drugs).
Pretty much everyone "likes" taking fentanyl once they've had it a few times, which is why they are spiking other drugs with fentanyl to create new users rather than asking "would you like fentanyl with that?"
Economics question: if Novo Nordisk and Eli Lilly have competing GLP-1 drugs, why hasn't competitive pressure driven them to offer their respective product nearly as cheaply as the compounding pharmas? Can't be insurance if almost nobody's insurance covers it. So if NN and EL are competing with each other, AND the compounders, what accounts for the vast price difference? It can't be 5-10x more expensive to add bacteriostatic water the way the FDA would like you to, can it?
Someone asked the same question up thread with more in depth answers but TL:DR - competition between two parties is just called Iterative Prisoner's Dilemma, and we all know that there are non-defect strategies for that.
They're different products as well, though? So some people will do better on Ozempic/Wegovy, and some people will do better on Mounjaro/Zepbound due to different tolerance of side effects etc. The pie is big enough to carve up different slices of the market. If I'm losing weight on Ozempic, I don't need to go on the Eli Lilly product. Conversely, if the Novo Nordisk product is not helping, then I switch to Mounjaro. No reason to cut the prices of either to the bone since the potential numbers of customers is enough for them both to have half of the market each and still turn a tidy penny.
If it were the case that both products were equally effective and equally free of side effects, then yeah it would be worth competing on "our drug is cheaper". But as I said, some people won't be able to tolerate product A/B and so will have to try product B/A.
These compounders are now doing to medication what the piratebay / megaupload was doing to movies and music: They are distributing something in violation of a license illegally.
I remember the ferocity with which the US government prosecuted Kim DotCom, it's interesting to see that the same reasoning is not applied here, or could Denmark have the owners of these companies extradited?
Megaupload caused $500m in damages, I would assume the lost revenue here is much larger.
I think Scott is wrong in his analysis of changes in formulation the compounding pharmacies introduced. The compounding quality Act makes this exception to the "do not make copies of marketed products" rule,
unless there is a
change that produces for an individual patient a clinical
difference, AS DETERMINED BY THE PRESCRIBING PRACTIONER,
between the compounded drug and the comparable approved drug." This, in essence, off-loads the problem to prescribing practitioners. And good luck to suing one of those multiple nurse practitioners who do the prescribing. This will take months, if not years
I'm confused about the nature of pharmaceutical manufacturing. So one the one hand it's this incredibly expensive and resource intensive process such that it takes years for Novo Nordisk to scale up production to meet demand for these drugs, with prices remaining high the whole time... and yet apparently it's actually pretty cheap and easy for anybody to manufacture the same thing if we just don't block them from doing so via patent law? Couldn't Novo just license some of these other companies to manufacture the drugs in exchange for a cut of the profits rather than having to build up all of its own manufacturing infrastructure if that's the situation?
The incredibly expensive and resource intensive process is developing and testing the drugs in the first place. Especially the testing. Once you know with sufficient confidence that a specific arrangement of atoms will have the desired effect, producing that arrangement of atoms in vast quantities is *usually* pretty cheap.
But it typically costs a billion dollars or more to get to that point. Most of it "wasted" on failed attempts, but it's only by doing the expensive testing that you can ever know that.
The costs of development aren't really the issue, what I'm confused about is why Novo isn't able to ramp up its production quickly enough to supply demand now that that development process has completed, and yet these compounding pharmacies can apparently start producing tons of the drugs instantly.
Cant remember where I read it, but apparently the self-injecting pens were the bottle neck. Not manufacturing the pens, but setting up the sterile factory that put the semaglutide into the pens.
Novo could license these companies to sell their drugs into the US and European markets, but normally the FDA and its peers wouldn't license them as safe manufacturers without a substantial investment on their own part.
The implication being that the FDA has a lower safety standard for companies producing a drug during one of these official shortages, in addition to allowing them to manufacture drugs they don't hold the patents for?
The FDA isn't really in charge of enforcing the patents in the first place, although they might have a policy/regulation against devoting agency resources to verifying the safety of an unlicensed manufacturer AFAIK.
Really it seems like even under the declared shortage, the only thing that wasn't in at least a legal gray area here to begin with was the actual action of the compounding pharmacies measuring out the raw peptides and adding clean water and preservatives.
Scott, something I think you should investigate relative to weight loss and cardiovascular disease is a fructose- and sucrose-free diet. Doctors tend to steer patients towards low-fat and low-saturated-fat diets, but if you actually look at the literature, the evidence is way stronger that limiting fructose is good for your weight, cardiovascular health and levels of visceral fat, vs. a low-fat or low-saturated-fat diet. Yet for some reason the concept of a low-fructose/low-sucrose diet never seems to have reached patient recommendations or the public imagination. I've been trying it and I've already lost nearly 10kg, and feel better also.
BTW I tried ozempic but it made me very depressed and reduced my energy.
What we've learned from the compounding pharmacy interlude is that these drugs should be administered with vial and syringe, similar to insulin, rather than with limited dosage range obtained with the commercial injector devices. They should often be started with lower doses and adjusted with much more flexible increments and intervals in accordance with the patient responses. This can be accomplished to some extent even with the commercial injection devices by mechanically adjusting the amounts delivered.
Banned for this comment.
To subsidize you!
More seriously - because of a combination of not having socialized medicine (so we have to pay for our own drugs) and because the US doesn't do nationwide bargaining with drug companies (and therefore gets much worse deals). In the end this looks like US customers paying higher prices, subsidizing pharma research which everyone else then takes advantage of.
The US makes it illegal to buy the drugs in the EU at your low prices and ship it over.
What we gain from this is the entire point of what we're supposed to get from patent law enforcement in general. Patents, and their enforcement, incentivize companies to spend lots of money to innovate.
If the patent law wasn't enforced for Ozempic et al, then people would get these drugs for cheap. But that would also mean that companies like Novo Nordisk would not be incentivized to spend money developing the next generation of drugs. That's the tradeoff we make with patents: for 20 years, the company gets a monopoly and gets their huge profits, incentivizing them to spend money on R&D. After 20 years the patent expires and everyone gets their drugs for cheap.
Why is the optimal amount 20 years and not 10 years and not 15 years and not 30 years? A good solution is to have the length of a pharma patent depend on how much further investment the company does in new research after a drug comes to market, so for example if drug X cost $100 million to bring to market then the government gives a patent of 10 years with a 1 year extension for every $10 million the patent owner can demonstate it has done on further new research up to a maximum of 20 years.
This way pharma companies are directly incentivized to put money into research rather than the current method which I suspect is less efficient overall.
I don't claim that 20 years is optimal rather than 15 or 25. The optimal length of time for patents is very hard to estimate, as any experiments one would do with that number would have to be conducted over extremely long timescales, timescales long enough that the actual effect of innovation, and thus the relevance of those experimental results, would change over the course of the experiment.
Changing the length of patents based on how much money companies spend on research might sound like a good idea, but it's actually a bad idea because it creates bad incentives.
Currently, patent law rewards inventions with compensation (monopoly on using the invention) proportional to how useful the invention is, not how much effort is spent creating the invention. If company A spends $1 developing an invention that generates $10/year of sales, and company B spends $10 developing an invention that generates $1/year of sales, then company A gets effectively reimbursed more by the patent system (although both companies make their money back with a 20 year patent timeline). The patent system gives rewards proportional to the value if the invention, not proportional to the amount of money spent inventing. Therefore, companies are incentivized to produce the most useful inventions, not directly incentivized to spend the most money on inventing. That's good because that's the end result: at the end of the day, we want useful inventions (we all get them for free after 20 years!); we don't directly want money spent on inventing because that's just a means to an end.
If the patent system rewarded spending money on R&D by indirectly reimbursing that money as you proposed, that would shift the incentives away from inventing useful things to incentivizing spending more money. That would be bad: really what we want is for useful things to be invented, so we should design a patent that incentivizes that above all else. Under your system we would probably see a lot more money being poured into useless dead end projects that will never work because the companies have less incentive to be stingy with their R&D money and less incentive to maximize the potential impact of their inventions. We would see fewer useful inventions per dollar spent on R&D.
If we didn't have patent law, it's not the case that we would all get Ozempic for cheap. Instead, we wouldn't get Ozempic at all! Because no one would have ever spent the money to develop it in the first place.
The patronage of politicians who are in the pocket of pharma corps, I would assume?
Like, 'why does the government not oppose these oligarchs' is a question that affects every domain of policy and politics, and it generally has about the same answer in every case.
The answer is, of course, that communism doesn't actually work?
That's a false dilemma.
If only...
I'd take communism over feudalism or anarchy, so I'd probably refine that to, "communism doesn't actually work [well]."
Every time someone criticizes the wealthy and their control of teh system, someone jumps in the comments to say 'yeah but communism is worse so we shouldn't do anything about it'.
You are the only person here talking about communism, and it's entirely irrelevant to the conversation.
The real reason is because the voters don't force them to. There are many reasons for that, including a significant faction that admires oligarchs.
The voters only have two realistic parties to choose from, thanks to the mess that is first-past-the-post voting and the way it enforces a two party system.
If both parties are sucking up to oligarchs, the voters have no way to express their anti-oligarch sentiments through voting.
Of course there are. There's polling, for example. That does matter to politicians and their campaign staff. Is there evidence that very many voters care about the issue at all?
I've found that a higher dose of Zepbound once every two weeks works pretty well. I'm sure the brightest minds at drug companies are working on a way to make this impossible as we speak.
Do you have a PK/PD rationale for this? How much higher?
Right now 7.5mg when I was doing 5mg. I think I'll go up to 10mg the next time I talk to my doctor. I don't have any rationale except that once a week felt like it was hitting me pretty strong (nausea, I had some bouts with diarrhea that may have been related/exacerbated by the zepbound), and since the price is the same, why not just drag it out until I start to feel hungry again?
I also feel like there might be something to the idea that when trying to lose weight putting your body (or at least my body) on a bit of a rollercoaster is better than letting it adjust to a steady state. In the past, I've had success switching to carb-loading when I plateaued trying to lose weight.
Also it's nice to have a day or two to remember how good food can taste and how much I enjoy it.
Makes sense! Thanks
Would love to have some mild aversion to food. I’m a few months in and wondering if the drugs actually work. About to take 10 mg because not a single symptom or side effect so far. Still eating everything in sight. Grr.
> Trump will invade Denmark over Greenland and seize the Novo Nordisk patents as spoils of war
I think this is backwards: the correct strategy is to threaten to void the patents in the US UNLESS Denmark cedes Greenland.
I know we're both joking, but I think if Trump voids foreign pharma patents, that gives the EU the right to ignore US patents, and the US gets the worse end of that deal.
aren't they sorta already ignoring them buy paying way less for the drugs than we do for *gestures vaguely at lots of complex things* reasons?
Not exactly. They bargain with the pharma companies, and the pharma companies sell them at very low prices. Partly this is because an entire country has a lot of bargaining power, partly it's because they know these countries are poor and can't afford to pay US prices, and partly it's because the pharma companies know that the countries always have the nuclear option of refusing the deal and infringing the patent so they don't want to play hardball. But the agreements are legal, the patents are being respected, and if they had legal permission to ignore the patents they would pay much less.
If the manufacturing cost is really in the $5 dose range, and if Bam-15 proves out (https://pmc.ncbi.nlm.nih.gov/articles/PMC7224297/) the companies better make every dollar they can before the market crashes under them. That seems consistent with what they are doing.
According to an Advisory Board report, the same patented drug from Novo Nordisk is $169/month in Japan, not exactly a poor country and $83/month in France (which is also not poor). Clearly the US is being fleeced - I'd honestly rather we paid Novo Nordisk the Japan or France price than we pay compounding pharmacies who didn't develop anything. Of course, that would take the government negotiating drug prices for us.
Novo Nordisk is Danish, and the shortage of ozempic in Europe at the start was because it sold for so much more in America, as well as the much bigger market, that it made economic sense for the company to go "Yippee!" and export everything produced to the US rather than sell it at home. They've since ramped up production to cover all the demand, but the free-riding was going the other way, as it were: because they can charge more in the US, that was where it made sense to sell the drugs.
This sounds like a win-win to me. If Trump wants to actually improve the economy (rather than just repeat Elon Musk's lies about the economy) he should do it. I'm sure "tariffs" will resolve any reciprocity concerns.
I think given the costs involved in pharmaceutical innovation, the reduction in incentives that this should cause would be a disaster even if pre-existing bad policies mean that the loss of profits would not be as large as it would be if Europe was like the United States when it came to medical prices.
As far as I can tell, the US economy is currently tanking. Or at least the stock market things so.
Tanking? A 6.8% drop in the dow over this last month? Not wonderful, but show me _one_ photo of a stockbroker splashed at the bottom of a skyscraper for me to take it seriously.
edit: A current photo, not 1939, and not photoshopped, AI generated, or otherwise synthetic.
Does it? Not that we should give Trump ideas but my expectation is that European pharma sales in the US dwarf US pharma sales in the EU.
You're probably wrong even dollarwise, but you might *become* right eventually if the FDA and NIH get fired hard enough.
It's probably a major loss for the US companies that produce the drugs and sell then in the EU. The EU has a population of 450 million to the US's population of 330 million per Wikipedia, so that more than doubles their market. And if the profit of producing and patenting new medications is cut in half, then there's less of an incentive to produce those medications. Not great.
The EU does have more people then the US, but American pay way, way higher prices for drugs then Europeans do. Looking it up, ~50% of world Pharmaceutical sales are in the US (as opposed to ~25% in Europe).
Based on recent experience I wouldn't expect Trump to be constrained by existing legsl approaches or internal coherence. He'll declare via executive order that gila monsters are US citizens so the patent alteady belongs to the USA, or it's being taken as reparations for Danish fentanyl, or something. And dare everyone to do anything about it
Bad deal for whom?
Due to weird Tax things I understand (Not an accountant) that even US Pharma companies barely pay any Taxes in the US.
https://www.npr.org/2024/04/12/1244509038/u-s-drug-makers-see-big-profits-but-many-pay-taxes-far-below-the-corporate-rate
But both American and European consumers win big, even if the pharma industry loses. Patents are in practise mostly a scam to transfer wealth from ordinary people to big corporations.
How much would Ozempic etc cost per month if there were no patents, and a free market?
To answer my own question, c. $5/week or $20-25 a month.
Unfortunately, an idea being stupid and counterproductive seems unlikely to stop Trump.
Lilly has rolled out a program of Zepbound vials for $499 a month if you are a cash payer to their direct pharmacy. They are closing in on the compounding pharmacies' price in any case.
I've heard stories of doctors prescribing and neat multiples of the dose of a short supply medication that the patient needs.
Like 2x the dose.
So the patient splits the pills and gets extra time to wait for pharmacies to resupply.
I realize you hate the FDA, but as they've already decided the emergency is over and you claim it's the pharma companies that will be enforcing this ban, I fail to see how DOGE firing the FDA has any effect except locking in the current status quo and ensuring no future emergencies are declared and no future drugs are approved?
I'm pretty confused as to whether it's the FDA's job or Novo Nordisk's job to go after telehealth startups and pharmacies illegally selling patented medications. My guess is it's a combination of both. Novo Nordisk might be the one who files the lawsuit, but the FDA will probably have to give some regulatory guidance that no, you can't really prescribe 0.51 mg and say you've gotten around the whole issue.
For the record, I think the FDA is acting correctly here.
There is also an argument that the way we do drug patents results in a net negative to society.
Make that "the way we do patents".
I'm not sure HOW they should be handled, and something related to the concept is beneficial, but what we've got probably isn't. If nothing else, the "reveal the process" part needs to be made EXTREMELY stronger.
As a person with a number of bogus patents ... the current US system is absurd.
I don't know *HOW* to fix it, but one thing that would be an improvement over what we have is to just limit the number of US patents granted per year. Require the patent office to stack rank the applications and only the top "N".
Google AI says the US granted about 350,000 patents in 2023. Maybe we try limiting the number to 10,000 - 20,000.
Note that this doesn't necessarily fix DRUG patents, but it is probably still an improvement over what we have. We can iterate from there (except not really because the US Congress is pretty bad at iterative law tweaking).
And I'm pretty sure that the patent holders right should be
"if anyone else tries to make this, they have to pay $X per Y".
So everyone pays the patent holder a fairly modest cut, and innovation can continue. Not any sort of outright ban on making patented stuff.
One possibility would be a prize for a treatment that solves a particular problem, much like the British Admiralty did with a prize for solving the problem of determining a ship's longitude at sea.
You forget take it takes years for the FDA to come up with guidance, and they are only "non-binding recommendations"
Someone in another comment says that FDA approval and patents are technically two separate things, and compounding pharmacies have technically been violating patents this whole time. So you might think that the disapproval of an FDA that couldn't do any enforcement due to DOGE stuff would be ineffectual.
In practice, though, it probably does matter. If the drug companies had sued compounding pharmacies during the official shortage, news articles would have mentioned that they're suing these companies for doing something the FDA has approved. But now, those articles would say that the compounding pharmacies getting sued are going against FDA regulations, so the optics might be a lot better for the drug companies now. In that sense, the FDA can exert a some pressure without actually doing its own enforcement.
So they have become a marketing arm for big pharma?
It doesn’t look that way to me, but I’m going to have to admit that I don’t understand exactly what the relationship is supposed to be between FDA approval and intellectual property. In any case, this wouldn’t be “marketing” – it doesn’t face customers at all. It would be more like mutual aid on regulatory and legal enforcement. Whether that’s a good thing or not depends on whether you think it’s good for those things to be enforceable.
I'm sorry, but I don't understand. News articles don't face customers?
Why don't insurance companies cover these weight loss drugs? I would think that the savings from all the obesity-related health conditions would be worth it.
(A quick google search shows a variety of conflicting answers.)
I think this mostly isn't true.
Many of these conditions don't cause problems until old age, and patients go off private insurance and onto Medicare at 65. So it's not worth it for insurance companies to spend money now to prevent a patient from having a heart attack at 70.
It might be worth the *government*'s time, but first of all, they checked and it isn't, and second of all, there's an awkward issue where from a purely economic perspective, the government wants you to drop dead ASAP, because seniors don't pay tax but do cost money in Medicare costs, so it's not always (from a purely economic perspective) worth their time to make you healthy.
I've thought about that in relation to smoking/social security before. I hate smoking, but I wasn't as mad at smokers after I learned that their early deaths make up for all their extra health costs. I guess I wasn't sure how many of the obesity-related costs show up before age 65.
It also seems that health insurance companies do care to a certain extent about some of these things--I'm nagged about once a month via email by my employer-based health insurance about their program to keep people from developing diabetes and I really want to email back saying "Leave me alone, I'm a skinny guy who runs a lot." But I guess that program is cheaper than brand-new drugs.
Huh interesting. I know that things like the British National Health Service spend more on preventative public health measures like anti smoking or obesity campaigns. On the basis it saves them money long run. Wonder why their economics are different. Maybe to do with owning the hospitals directly?
Well, it's entirely possible that one of the two governments simply did their numbers wrong, either re: the efficacy of the campaigns or the saved costs.
They have done the economic analysis in the UK and smoking saves the NHS money net because they die sooner. The govt. pushes anti-smoking to avoid sickness and premature death.
Is it just that they die sooner, and/or the billions raised in tax meaning they more than pay for their own treatment in aggregate? The last time I looked into it, the govt was a few billion £ up on net from smokers. Hence implementing a tax on vaping - not because vapers appear to cost anything (so far), but they're missing the billions in 'profit' they enjoyed from smokers.
The UK is a classic “single payor system” plus reimbursement is a consequence of approval that uses Health Economics to determine “value for money”. The net result is that many drugs remain unapproved in the UK (essentially rationing. See Leqembi for Alzheimer’s Disease) as an example.
The national health service is actually trying to help people, not maximise profits.
They have political constraints.
The NHS bears the cost of preventive treatment and the benefit of lower future healthcare costs. In the US, people change insurance companies frequently enough that some other insurance company is likely to receive that benefit, not your current insurer.
This is interesting. I think in Germany there's a system in place to make sure this doesn't happen, so that people don't get cheap private insurance while they're young then go back to public when the conditions start coming in.
Not sure how the German system works with low/no income though
People are usually auto-enrolled into public insurance and switching is generally only allowed in specific circumstances.
I don't know all the details but my impression is that you either have to be self-employed or making a bunch of money to be permitted to switch to private. Then you're generally not permitted to switch back, though there are exceptions.
The result is that the low / no income folk generally have public insurance because they don't qualify for private.
That is quite correct. Additionally less than 10 percent of the people in Germany have private insurance, as it is only allowed if you earn more than 70.000€/a.
Is it really so hard to design a healthcare system with incentives that result in improved public health?
It is when your other desiderata include things like "nobody gets preventative health care without paying for it" and "severance of a commercial relationship with a private health care provider also severs all responsibility for future health outcomes of their past standard of care".
Healthcare isn't health. But if we think broadly, there policies that can affect deaths from traffic accidents, homicides etc which cause the US in particular to have high morality rates.
Public health, or health of the public? Two very different things.
What's the difference?
It would bankrupt them to cover for everyone who qualified, Lilly and Novo are not cutting them big discounts.
"FDA regulations say that during a shortage, it’s legal for compounding pharmacies to provide medications without getting the patent-holders’ permission."
That's not correct. The regulations say you don't need the FDA's permission. The compounding pharmacies are still (probably) infringing the patents and are liable for that. I don't know why the patent holders have not sued, but my best guess is it would be bad publicity to sue someone for providing medicine when you yourself cannot provide enough of it.
Can you explain the difference between "don't need FDA's permission" and "legal" in this case? Why is the FDA going after patent-infringers for reasons other than patent-infringement?
Apparently, patent law and the FDA regulation of drug manufacture are separate considerations.
Perplexity says:
Section 503A of the Food, Drug, and Cosmetic Act allows compounding pharmacies to create medications that are "essentially copies" of commercially available drugs only if those drugs are listed on the FDA's drug shortage list. In such cases, the FDA does not consider the drug to be "commercially available," thereby permitting compounding under certain conditions, such as not doing so "regularly or in inordinate amounts". However, this does not exempt compounders from potential patent infringement claims under the Patent Act, as the FDA's permission to compound during shortages does not override intellectual property laws.
From what I remember from the Covid times, the FDA actually does more. When a producer builds a production sites for drugs, then the FDA checks that the procedures of producing the drug are safe, and that industry standards at this site are met. For a new high-tech medication like the Covid vaccines, I think this included visiting the site, checking that industry standards are met, and that the production protocols and the procedure for detecting production errors make sense and minimize the risk of contamination. This process is needed for every new production site, even if the company already has a few approved ones for the same drug. Though obviously the first site will be scrutinized a lot more.
I imagine that for drugs that are easy to mix with standard procedures, this is probably only paperwork. I guess the company needs to promise that it's not just a filthy kitchen, but that they meet common production standards. Like having someone who mops the floor once a week, and not producing two different drugs on the same table at the same time.
I don't really know, but it would make sense to me that "don't need FDA's permission" means that you are allowed to skip exactly this process.
All this is completely orthogonal to patents. One question is whether the produced drug meets the necessary quality standards. The other is whether the company is allowed to produce and sell the drug. Perhaps the FDA also check patents as part of the general approval process, but it's not the whole process, and probably only a small part (if it's a part at all).
The compounding pharmacies making “bootleg” ozempic aren’t regulated by the FDA, they’re regulated by state pharmacy boards. Drug manufacturing facilities for pharma, on the other hand, are FDA regulated and inspected.
The FDA does not enforce patents--that is completely done by the patent owner.
Actually, I've figured out a diet that actually works: Take in less calories than you burn.
Frankly, I would rather be somewhat overweight.
This. When I'm really sick, I don't eat because I don't want to and eating makes me nauseous. I easily can lose several kilos that way.
Then I get better, and I eat again, and whaddya know, those missing kilos come flying home! And my appetite hasn't reset so that I am now adjusted to eating less.
If there was some way to squash carb cravings, I'd have much less problems losing weight. Yes, I do eat salads, no I don't like mayonnaise, but what I need (or what my body tells me I need) with that is a bread roll, or two slices of bread, or something like that.
If I could give up eating toast or sandwiches, I'd lose weight, and I know this because I did lose weight when strictly restricting my daily carb intake. So why can't I just do that again? I don't know. Lazy, greedy, no willpower, stupid? Sure, fine, but that doesn't tell me *why* I want to eat a loaf of bread and not, say, a pound of steak or a whole chicken.
I usually tell low income workers to earn more than they spend and that's how you get rich. Works every time! ( Equally reductive and inane logic )
Yes, exactly—same as we tell alcoholics to drink less. Works famously, yeah?
I read the linked piece from Scott’s response, and it reminded me of a different book from around the same time, The Obesity Code. He mentions that telling fat people to eat less only addresses the proximal cause—just like telling an alcoholic to drink less.
The big question that some people refuse to acknowledge is: Why do some people have so much trouble eating less?
The recently chubby will explain it’s because of willpower or depression or tasty food. The chronically overweight know that there’s something else at work for themselves.
I was raising my eyebrows over people saying "just eat more salad" but now since I do this myself (and way more veggies and less carbs) I have to admit the are true. And it doesn't feel hard anymore. So it's more like good habits bad Habits. And it helps a lot for our whole life to find the good ones and get rid of the bad ones.
I once worked with a porker who dutifully ate salad each lunchtime at his office desk. But he lavished so much mayo on it, a third of a bottle each time, that the calories from that more than offset what he imagined he was saving by munching on rabbit food.
Unfortunately, this seems to work for some phenotypes and not for others. My body seems to get a good difference between eating something truly filling and a bowl of shredded paper (or a fresh salad). So, after eating a lot of salad, I get unbearable cravings for high-calorie things. I keep better shape on a high-fat diet.
That doesn't change the fact that ingesting less calories DOES work.
And if you actually take the time to discuss the issue with chronically overweight people, a hell of a lot of them won't even acknowledge that simple fact.
In the end any solution must address this base problem one way or the other. But if people aren't willing to acknowledge this as being the issue in the first place, they can't really find any solution to that problem.
"Why am I ingesting too many calories?" might have many answers. But agreeing that "too many" even is a thing is the relevant start of the search for a solution.
Reducing the problem to "eating" is already part of the issue for many. Many drinks also have a lot of calories.
And taking in less atoms than you emit works even better!
That's right. CICO isn't the end of the conversation, but it is the basis for the conversation. If you don't believe in the truth of CICO, you have no way to identify effective interventions.
Yes, you cannot get rich if you spend more that you earn. Low-income workers that successfully stopped being ones all did the same things:
- quietly quit the surplus sharing support network
- cut down all nonessential expenses
- invested their surplus into training themselves for a better job
How many calories do I burn?
You can calculate that pretty easily. Your basal metabolic rate can be calculated from your gender, height and mass. Add any kind of exercise/body movement to the equation and you know how many calories you are approximately burning.
This is warning that I will ban comments like these in the future. They're facile, suggest ignorance of an extremely long debate about exactly how this works scientifically and how to think about it philosophically, and are just going to make lots of people really mad. See https://slatestarcodex.com/2017/04/25/book-review-the-hungry-brain/ for a tiny part of the relevant debate.
Thank you. I was just composing a comment because I was "really mad." You said it better than I would, also.
I gave the guy a zap before reading Scott’s response.
Thanks for this policy.
If only substack could have like an optional reddit / lesswrong-style comment section...
Now that I think about it, why *do* so many websites have so bad comment systems?
*This* is where you draw the line? Do you think its fine in this case because its not political, or what?
https://www.astralcodexten.com/p/register-of-bans (URL buries the lede, it has the comment policy)
Thats the policy, but theres loads of comments which are at best true, and none of the others. This one on the other hand is very definitely true.
Three cheers etc. I'm still amazed we get comments like this EVERY SINGLE TIME the topic comes up.
This comment, while being non-chalant, simply states an objective truth. It's simply the first law of thermo-dynamics restated for an organism.
Accepting this base truth is really important; since any solution must address the problem. Why a person is ingesting too many calories must be figured out to devise a workable solution. But when not acknowledging that this is the base issue people can easily get distracted by supposed miracle cures.
There are many people out there who genuinely state that they don't know why they are obese as they are only eating "healthy" food. The mere fact that the amount of calories dictate weigth, regardless of whether a specific source of calories is considered healthy food, is truly ignored by many actual people.
So in the end, while each person might need a different approach, from a biological and physical standpoint it doesn't matter how you reduce your calorie intake: change of diet, change of habits, taking a 1000$/month drug ... unless the outcome of that reduction is to ingest less calories than you burn, you won't lose weigth! The importance of this statement can't be overstated IMO. That you, of all people, find this scientific base truth so offensive that you threaten to ban people stating it, is really concerning to me.
ANY argument on how to address a weight problem must in the end always address this core truth. There is now way around it. And any proposed solution can always very easily be quality checked by evaluating whether it's achieving this very simple goal.
Trying to supress this core truth is not conductive to solving the obesity epidemic.
*Your* comment is fine, his isn't. I think the difference is the time and effort you put into writing a post that engages the issues in some depth, while his didn't.
A helpful metaphor I heard - if you're such a fan of the first law of thermodynamics, why even worry about calories? You can just think in terms of *mass*. Presumably drinking lots of water will increase your weight, and drinking less will decrease it. There, problem solved!
The reason this isn't true is that the body regulates its weight very closely. If you drink a gallon of water (=8 lbs), you won't permanently gain 8 pounds. You'll just pee it out over the next few hours.
In the same way, a healthy person who eats too many calories will just lose the calories somehow. Some of this will be feeling full until they eat fewer calories later, some of it will be increased drive to exercise, some of this will be increased metabolism, and some of it will be weird things most people don't even think about (apparently your body can vary its caloric burn rate by ~400 calories daily just by fidgeting more or less, in a way that the average person wouldn't notice).
An obese person who tries to eat fewer calories than their bodily regulation system wants will then gain those calories back somehow, either by being so hungry that they give in and eat later, or by feeling more urge to exercise, or by metabolizing or fidgeting less. These effects are natural-seeming enough and powerful enough that "just ignore the drives using willpower" is about as effective as "just use willpower to hold the water in and never pee it out".
(this isn't 100% true; in healthy people the regulatory system usually has some slack, and with enough slack you can actually do quite a lot with willpower - but by the time we're talking about GLP-1 drugs we're probably talking about people for whom the regulatory systems are pretty broken).
This is why there are so many drugs that can make people gain weight (eg antipsychotics) or make them lose weight (eg GLP-1s). It's why people report so much variability in dieting (the same diet, followed when I was 25 vs. 35, had very different effects on my weight!) Understanding these systems is table stakes for talking about nutrition at all, and one reason that nutrition conversations on the Internet are so dumb is that they're constantly interrupted by people who are proudly ignorant of them and interject "But thermodynamics!" when other people try to hold useful conversations.
I've written more about this at https://slatestarcodex.com/2017/04/25/book-review-the-hungry-brain/ .
>An obese person who tries to eat fewer calories than their bodily regulation system wants will then gain those calories back somehow, either by being so hungry that they give in and eat later,
This completely dodges the premise. The person who gives in and eats could, in the alternative, not give in and eat. I can absolutely, 100% guarantee you that someone who eats 50 calories a day (to include essential nutrients) will lose weight over the course of 6 months. Do you deny that it is physically possible for a person with agency to construct a scenario whereby they eat 50 calories a day for 6 months? Is devising a device that prevents someone from driving to the grocery store or ordering food online really in the same universe of physically impossible feats as “holding in your pee forever”?
Somewhat related, but the only diet that has worked for me is not Keto, but Chinese Keto. Imagine Chinese food with no rice. It wasn't just that I was happier eating the food because I liked it, but there seemed to be some biological effect making me feel more satisfied and full when I ate Chinese Keto specifically. I'm guessing this somehow came downstream of what I ate growing up - maybe the kind of enzymes my body was already used to producing? Not sure, but I would've never figured that out if I just stayed on the CICO train.
No, you can't just think in terms of mass, as you own metaphore demonstrates. Drinking lots of water will increase your weight in the same way as picking up a dumbbell will. Your body can't store water and water is energetically neutral to your body. It can't build a single cell from you drinking water. What drinking lots of water will do instead is that you deplete your body of minerals. And resorbing water from your intestins and removing it from your body through your kidneys and urine actually consumes energy. So at best drinking lots and lots of water will actually make you loose weight in the long run (in a very very unhealthy way). Which you just admit yourself in the second paragraph. So why did you make this absurd point in the first place?
"In the same way, a healthy person who eats too many calories will just lose the calories somehow."
Sorry, but no, this is just plain wrong. A healthy person will absorb every single calorie it can. The amount of calories required for the body to function will be consumed right away, and every other calorie will be stored. Which is just a fancy way of saying that the body will turn it into cells. And those cells will be fat cells. You can turn those into muscle cells, if you exercise a lot. Which is why muscular people also have a high BMI without actually being obese.
Your body doesn't have many options for getting rid of excess energy. There is only three in total.
Option 1: not absorbing the calories in the first place. This is actually an illness and pretty dangerous for the people affected, if it is permanent.
Option 2: increasing the body temperature. This also isn't a real option. If it increases the body temperature by much, we call this fever. And if we increase it too much, you simply die.
Option 3: muscle movement. Unless you are execising, the only way for your body to move muscles is to shiver. I don't know of many healthy people who shiver without being cold. But you are the medical professional here. So maybe you know something I don't.
So no, your statement is just plain wrong.
All the ways you continue to describe on how healthy people get rid of excess calories don't fit the discussion. Because you are essentially claiming that excercise will deal with it. At which point those calories are no longer excess calories. They are actually required by the body to perform the excercise. A healthy person who is eating MORE calories than required to perform all body functions will inevitably gain weight. That's what the first law of thermodynamics demands.
"An obese person who tries to eat fewer calories than their bodily regulation system wants will then gain those calories back somehow, either by being so hungry that they give in and eat later,"
Which is exactly what the OP stated. You can't gain weight without actually ingesting those calories. What you are trying to claim here is that those calories don't count because "something something". But that's besides the point. Yes, life isn't fair. And some people have a harder time not ingesting more calories than they need than others. But that doesn't change the fact that the problem is those calories being ingested. And that you need to find ways not to ingest them.
Which is why drugs which diminish your appetite even work in the first place. If it wasn't about those calories, those drugs would do nothing.
And by obscuring those facts on purpose, you are simply spreading misconceptions.
In this comment threat alone I read that some contraceptive made a person gain weight. How many calories exactly does this pill have?
I read people claiming that a high calorie diet would make them lose weight. What they actually meant is that a high fat diet was better at saciating them than a high card diet. Which is actually helpful to know. Getting rid of those french fries actually is a lot more helpful than getting rid of the steak. Especially if combined with lots of fiebers; read fiber rich vegetables like salads, cucumber, tomatos, etc.
"one reason that nutrition conversations on the Internet are so dumb is that they're constantly interrupted by people who are proudly ignorant of them and interject "But thermodynamics!" when other people try to hold useful conversations. "
IMO the exact opposite is true. People willfully ignoring that fact leads to a miriade of misconceptions which leave people helpless and essentially force them to buy a 1000$/month drug. Because apparently that's the only possible solution (which it surely is for some people). When in fact many people actually have alternative options.
The core issue is that people have a misconception about how nutrition works. 7000kcal ingested in excess to what the body needs essentially translates into 1kg/2lbs of body weight gained. Which mean that if you eat half a cheese sandwhich per day in excess of what your body needs, you will end up at 300+lbs within only 10 years. Little things matter!
And so does the truth. Which you are obscurring here on purpose. Nothing a wrote is news to you.
>An obese person who tries to eat fewer calories than their bodily regulation system wants will then gain those calories back somehow, either by being so hungry that they give in and eat later,
That's calories in, calories out! Giving in and eating later is the thing we want to avoid, because CICO!
>or by feeling more urge to exercise,
[Pretty sure you meant "less urge"]
That's calories in, calories out! Not exercising, even though you should, is the thing we want to avoid, because CICO!
Whether we avoid those things through willpower (works for some, not for others) or fantastically expensive drugs (works for almost everyone if they can afford it), or things like bootcamps and subscription diet services where the "willpower" is external, we're avoiding them because taking in fewer calories than you expend causes weight loss.
That's really interesting. I've always wondered if someone can eat more calories than they need, and not gain weight.
Are by default all calories processed? Is there some system were your body just starts passing, rather than fully absorbing calories?
nit, probable typo:
>An obese person who tries to eat fewer calories than their bodily regulation system wants will then gain those calories back somehow, either by being so hungry that they give in and eat later, or by feeling more urge to exercise
"more" should probably be "less"
With the drugs that cause weight gain, how does this typically work? Do people eat more calories? Does it lower their metabolism? Do they become more lethargic?
Right. It's true, and it's arguably necessary.
I read through the article and the lipostatic baseline article tracks with my experience; if I gain a few pounds I mentally feel fat pretty much immediately and quite quickly shred it from portion control. I've maintained within the same +/- 5 pound range for the past few years without much effort, despite highly variable levels of exercise. This includes a month on the potato only diet that was mentioned here a few years ago; I thought it was quite good but then I had a family trip where I could no longer maintain it, culminating in a large ice cream that my potato gullet was not ready for.
However, I don't see how that doesn't square with CICO. It very much is a willpower thing; I weigh myself, see that I have gained weight, feel bad about it, and actively reduce my calorie intake to get rid of it. I also quite obviously employ willpower to firmly avoid high calorie junk like soda (NEVER) and candy (NEVER); I have a drawer full of candy that I get for holidays office functions etc. that I just awkwardly hold on to because I refuse to eat it. Conversely, if my weight goes down a bit I'll fine eating a bit more and will gain a little bit back to normal.
Is that not calorie in calorie out? I do maintain my lipostatic baseline per your book review, but I fundamentally do so by experiencing the qualia of body weight in proportion to my lipostatic baseline (which self reinforces due to my own conscious bodyweight expectations) and manipulating my calories in/out accordingly.
My experience is that the main objection to CICO or more generally "diet & exercise" is that it isn't a question of mere willpower, but that some people have naturally high weight set points and if you eat fewer calories than will keep you at that point, you would be unbearably hungry. But in this post, you mention this study:
"In 1965, some scientists locked people in a room where they could only eat nutrient sludge dispensed from a machine. Even though the volunteers had no idea how many calories the nutrient sludge was, they ate exactly enough to maintain their normal weight, proving the existence of a “sixth sense” for food caloric content. Next, they locked morbidly obese people in the same room. They ended up eating only tiny amounts of the nutrient sludge, one or two hundred calories a day, without feeling any hunger. This proved that their bodies “wanted” to lose the excess weight and preferred to simply live off stored fat once removed from the overly-rewarding food environment. After six months on the sludge, a man who weighed 400 lbs at the start of the experiment was down to 200, without consciously trying to reduce his weight."
This suggests that one of the following must be true:
(1) Anyone can lose weight without feeling unbearably hungry just by restricting the *types* of foods they eat.
(2) While this works for the nutrient sludge, this doesn't work if you loosen your restrictions to foods like potatoes and chicken. You really have to eat nutrient sludge, and this is an unreasonable diet to expect of people.
(3) Even the availability of non-sludge-like foods causes this diet to fail: having the ability to go to the grocery store and buy delicious calorie-dense food would make you unbearably hungry in a way you wouldn't be if you're forced to eat the sludge.
(4) The study is false, and the people were really unbearably hungry.
I'm unsure of which one you believe. I get that just citing CICO elides a bunch of important details, but this study really seems to support the CICO/willpower view and I haven't seen a great reason why that's not the case.
CICO and willpower isn't the same thing though. I don't think that being obese is the result of a moral failure of the person affected. But it still is caused by consuming more calories than required to maintain a healthy weight. Thus the question becomes what to change to reach a healthy weight, and more importantly, how to maintain it longterm afterwards. Because most people can lose weight, if they really want to. But maintaining it is more difficult.
And honestly: spending 1000$/month for a life time to me seems as ridiculous an option as the nutrient sludge dispenser one.
My, aren’t you self-satisfied.
Well, Bob, for the first 25 years of my life I was someone who naturally stayed slim. I did make some very minor efforts to avoid gaining weight — like not eating desserts, and not keeping cookies in the house — but I wasn’t perfectly consistent even with those very mild restrictions. It didn’t matter. My weight always stayed in the same slim-but-not-thin 10 pound range. Then I began taking birth control pills, and my weight went up 20 pounds in 2 years. It took me a while to suspect that the bc pills were the culprit, and before realizing the pills had caused the weight gain I tried quite hard to eat fewer calories and exercise more. I had the same experience most people do: It turned out to be surprisingly hard to stick with this plan. I’d stick with it consistently for a while, using a LOT of willpower to do it, and lose 5 lbs. Then over the next couple weeks I’d gain it back.
Then I stopped the bc pills, and over a summer lost all 20 extra pounds with no effort at all. I did not follow a diet or count calories. I just wasn’t very hungry. I then returned to staying in my previous slim range with no planning and no serious effort.
I now understand better people who are overweight and can’t lose the weight. I think many of them have bodies that, like mine, tend to have a stable weight — except their stable weight is high, while mine was moderate to low. So stretch your mind a bit, Bob, and try on the possibility that the reason you maintain a normal weight is that you are lucky, not that you have more common sense of willpower than overweight people. Then maybe you won’t be so inclined to say sneery shit when people talk about having trouble losing weight.
This is going too far in the other direction, and is also just as snarky in an equal and opposite manner. As someone who managed 15kg of sustained weight loss by examining the various factors that went into my weight gain and reversing them, just like you did, I think that a purely defeatist "there's nothing to be done" attitude isn't any more helpful than a blindly optimistic one.
You may have examined the factors, but I did not. I had one real factor, the bc pills, and I can't even remember how I came to the idea that they might be the cause of the weight gain.
But before I figured out that I should try stopping the bc pills I did think of some of my habits (which were the same ones I'd had when I easily stayed slim) as factors. lI did not exercise systematically. (On the other hand, I got around entirely on foot and by bike, in a place where home, work and stores were not particularly near each other.). I did sometimes buy a muffin with my coffee. I liked to put honey in my yogurt and my tea. I sometimes pan fried things that could have been baked. These habits I thought of as the factors that had caused my weight gain.
And when I tried to lose the 20 lbs while still on the BC pills I did make a big effort to change all those things. But it was terribly hard to stick to. And, like most people, I have done some hard things that have taken sustained effort. I wrote a dissertation. I adopted a child as a single woman and homeschooled her while holding a job. I have done backpacking trips in the sierras, carrying my tent and food and water on my back, walking uphill all day long on the first day, as we ascended. . But nope, I could not lose those 20 lbs while taking bc pills.
Not eating as much as your body is asking you to is hard in a different way. It's not a matter of simply putting up with some periods of hunger. There is a constant undertow towards food that goes on, even when you are not feeling hungry. Your body thinks it needs more food, even if you think it does not, and it exerts pressure in all kinds of ways, just as it does when you short yourself on sleep. It becomes vigilant for food cues. It plagues you with food images. It attacks in the middle of the night when you get up to pee, suddenly insisting that you can't bear not having a bowl of cereal.
I am sure there are people who truly are lazy and self-indulgent, or unable to analyze factors and make an effective plan, but there are plenty of people who are stuck with being overweight who very obviously are able to identify factors, plan, and follow a hard plan. *Scott* struggles with overweight! I am sick of people who think that if they can be slim, everyone else can, or even, like you, that if you can lose weight, they can. They are not you. If they could have, they would have.
There is only one line of snark in my answer to Bob -- the first line -- and I think he richly deserved it.
I'm not sure what you mean when you say you didn't examine the factors, and then say that the pills were the major factor for you. That sounds to me like you found the major factor behind your weight gain!
For me I quit my stressful job, moved back from the US to Australia, and began walking everywhere again. None of these took effort to maintain: it was all upfront costs in the form of changing my environment. This made me drop about 5kg without even thinking about it. I then calorie counted my way through another 15kg drop because I was bored during COVID, regained 5kg over about a year, and stabilised just below the top of the healthy BMI range.
I understand that starving yourself is difficult. I did it out of boredom because I was in the middle of lockdown and it was still hard. I just...don't think it's impossible, or totally ineffective for 100% of the population. What I found was that eating at a deficit taught me how to optimise my food intake so that it was the most satiating for the least calories, which is something really valuable that I still use today.
Seeing people be so dismissive of an approach that worked for me feels like it could turn others off approaching weight loss by trying different things. It feels like learned helplessness. I know that I can't grab everyone by the hand and show them the 1995 satiety index, or the studies on fibre and gastric emptying, or that blog post about liver energy use and dietary protein, but I can at least say "hey, learning stuff about weight gain and loss sometimes works, no guarantees of success but also none of failure."
The problem isn't that people eating to many calories would be lazy or self-indulgent. The problem is that they are ingesting too many calories. Any kind of moralization doesn't help with the issues. Figuring out WHY they ingest too many calories does.
In your case you figured out that this pill changed your perceived hunger in a way that made it exceedingly hard to maintain the weight you wanted to maintain. But you understanding that you were ingesting to many calories was still important. It just took you a while to figure out why this changed for you, when you had no such issues before taking that pill.
Other people have other circumstances. But the main factor remains: the amount of calories must somehow be brought down. Whether this is through intermittent fasting, a change of diet, the use of one of the three substances the article above mentioned, pure will power or any other means doesn't really matter.
There is no silver bullet to solve everything. But understanding that the calorie intake must change, and then devising a solution on how to do that, is what's leading to a solution. Your BC pill was entirely elective, so you were able to just change that. Other medication has similar effects, but isn't elective. On such scenarios one can blame the medication, but that won't solve the issue. Finding alternative solution to reduce calorie intake does.
That's why trying to suppress this core issue is so hurtfull to the conversation. As is blaming obesity on some moral failure of the individual. But the solution to the later isn't the former.
i’m fairly overweight and am slow to lose weight so i have to make a lot of effort to even maintain my current weight, but lifestyle (barring other medical issues) is obviously the only way to sustainably lose weight. nothing is wrong with me and i’m fairly active and eat well, people just have different metabolisms and have to live accordingly. i think being realistic about it (without wallowing in pity or blaming yourself) is the only solution—only you can make yourself healthy, not any miracle drug.
more and more research is showing that glp-1 agonists definitely cause temporary vision changes & might be linked to increased risk of blindness (it had been known to worsen diabetic retinopathy this is a potential link to NAION in otherwise healthy individuals.) blindness in severe diabetics would be an ok trade off—it just worsens the symptoms while controlling everything else—but not in obese but otherwise healthy individuals.
the free market and a loose regulatory approach has in fact failed by making an expensive “miracle drug” whose risks are not completely understood & produces patients reliant upon them for life so widely available.
Yeah, I know about that. But are you aware of the stats for improved odds regarding many
bad illnesses and systemic conditions people on these weight loss drugs have? Some are downstream of weight loss, some seem to be direct effects of the drug. I’ll bet the reduction in HbA1C (a blood sugar measure) alone on these drugs way offsets the risk of blindness from glp1 agonists. Google “H1C As predictor vision loss” and you will find many recent studies. Here is one: https://bmcophthalmol.biomedcentral.com/articles/10.1186/s12886-022-02608-3
Seems to me you have an attachment to the idea that dieting is the only safe approach to the problem of overweight, and have seized on these findings about vision problems in, so far, a scattering of patients. And you’ve failed to consider other info, which is very well known, that must be considered when evaluating risk/benefit ratio of these drugs.
This actually does not work, because of the large variance in how much nutrition different people with different digestive systems get from the same food with the same number of calories listed on the box.
Of course, you could update your claim to 'digest less nutrients than you burn', but then the obvious reply is that we have no way to reliably measure either of those things on an individual basis, so it's impossible to follow that advice in a practical manner.
>Of course, you could update your claim to 'digest less nutrients than you burn', but then the obvious reply is that we have no way to reliably measure either of those things on an individual basis, so it's impossible to follow that advice in a practical manner.
As long as your body obeys the laws of thermodynamics and can't create calories out of nothing, you can always reduce your intake until you start losing weight. As for following that advice in practice: use a scale.
How would you feel if I told you "whip yourself bloody every 30minutes, every day, for 6 months or even multiple years"?
That's what you're saying. That's what "just eat less" is. You're telling people to torture themselves constantly so that at some point in the distant future, they'll maybe look a little bit better.
No, I'm not saying that. I've been replying to user "darwin" and his claim that it's literally impossible to count calories because of variance in digestion. If your personal digestion is that much different from what's printed on the food packaging, then maybe take responsibility for the variance in your body because who else can? Find your personal conversion factor, apply it, and keep updating it. Do some basic science if it helps, write shit down: how much you exercise, how many calories you consume (purely as per the packaging), how your weight changes in response. Nobody is asking that you get the caloric balance right down to single digits or every single day without fail because that would be insane to even try. Just realize that weight control is a marathon. Look honestly at what you're doing in the long run and what effect it has in the long run.
Just because you're groping half-blindly towards the goal doesn't mean you can't reach it. Just don't close your eyes entirely, which I know is tempting when everyone keeps telling you how hard it is for this or that reason.
Most people could lose significant weight without torture.
How seriously do you expect anyone to take a comparison of "reduce your intake of food in a controlled manner" and "whip yourself bloody every half hour"?
Yes if you eat zero food you will lose weight until you die. This is not a useful insight.
It actually is useful, because it means that a) not consuming calories results in weight loss and b) the body has a certain rate of consumption of calories at all times.
From that you can conclude that there is some amount of calories (potentially a range) that equals the consumption of calories of your body, at which point you will neither gain or lose weight, and if you consume less than that amount, you will lose weight.
You would be surprised how often I have to have this discussion just to disentangle this most basic mechanic of weight loss from the very different and more complicated problem of how to sustain that weight loss. If you do disentangle these two things, it might let you focus more on the latter.
It doesn't just work in theory. It also is scientifically proven to work in practise. Whether you switch to a diet that keeps you saciated for longer, or whether you skip meals consistently, doesn't really matter.
See for example: "Intermittent fasting and health outcomes: an umbrella review of systematic reviews and meta-analyses of randomised controlled trials"
https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00098-1/fulltext
That's a bit like saying the it's easy for humans to fly: just exert more force upwards than gravity pulls you down.
"Actually, I've figured out a diet that actually works: Take in less calories than you burn."
I'm trying to provide a helpful response so please take it that way.
For many/most overweight people, your "Take in less calories than you burn" is equivalent to "Inure yourself to being hungry all the time."
If you find the second formulation to be helpful then I would suggest using it rather than the first. The second has the virtue of acknowledging why the first is empirically so difficult.
If you find the second formulation to not be helpful then maybe don't offer the first?
> Inure yourself to being hungry all the time.
Yes! That's the whole thing. If you pace your meals so you don't ever think, "oh, it's 7pm already, I guess I'll go eat", but instead think, "oh, I'm quite hungry, I am looking forward to dinner at 7pm", then you will lose weight. And it has to be stomach hunger, not head hunger. Your goal is to learn not to silence this sensation with a snack, but to revel in it, the way people enjoy the heat and cold of a sauna or muscle soreness after a good workout: "oh, I feel properly hungry, this means I am eating the right number of calories and will enjoy my next meal".
In my experience even as a naturally slim person, you don't have control over whether you feel hungry. You may THINK "oh I already ate a lot, I shouldn't be feeling hungry again so early" or vice versa, but the body often has other ideas, and it will get increasingly insistent the longer you try to ignore it.
> and it will get increasingly insistent the longer you try to ignore it
That actually doesn't track with the experience of people trying that. Wether it's "Alone", "7vsWild" or other experiments where people try to survive in the wilderness for an extensive period of time, all of them unanimously report that the feeling of hunger goes away after 2-3 days and only resurfaces in waves.
That's actually what you'd expect to happen, because otherwise our ancestors wouldn't have been able to successfully hunt once they went into a caloric deficit for a day or two ...
I didn't say you have control over you feeling hungry. The point is to recognize the sensation and reinterpret it. If you get off a stressful conference call and go buy a snack bar to calm down, that's not real hunger, you have to recognize it and stop yourself: "I am not hungry, I am angry".
And you do the same with real pangs of hunger: "I am hungry, this means my diet is working, this means I am transforming my body into the body I want, every minute I successfully resist these pangs until the next meal brings me closer to the result I want, not feeling hungry so close to the next meal actually means I've overeaten".
And you do the same when eating: "I've eaten as much food as I need, the only reason I want more is because satiation hasn't kicked in, instead of reaching for more I should wait until it does".
How about "hungry for a few hours a day"?
Intermittent fasting works very well for me. I eat at most 8h a day; meaning I don't eat anything for 16 hours a day. Yes, sometimes, rarely, I still get hungry late in the morning. Waiting one to three hours for lunch isn't that much of a challenge though. It mostly only happens when I skipped dinner as well anyways.
I've been doing it for almost three decades now. It works very well for me. Whenever I'm on vacation and don't do it due to me always having breakfest with the family, I start to gain weight. So I'm not magically thin.
Intermittend fasting has been extensively studied. It doesn't just work for me: https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00098-1/fulltext
If that was true, the article above wouldn't exist. The drugs described clearly managed to make the people taking them "take in less calories than they burned". That's how they lost weight.
If you actually want to lose weight the obvious follow up question would be "How?".
Then the next step would be to investigate all sources of calories consumed and to determine whether an adjustment there would be feasible and helpful. If it is, fine.
If it's not, the next question would be if an adjustment in life style would help. Can you limit accessibility to snacks? Can you do some kind of fasting like intermittent fasting? Can you reduce consumption of heavily processed foods and takeout? Can you eat more slowly with frequent pauses to give your body time to process and report?
If that didn't help the next step would be to investigate your medication (if you are using any) for stuff that's known to mess with the metabolic feedback loops. And, if you happen to take any, to research wether substitutes are available.
If that's not the case the next step would be to look into possibilities in increase exercise. This usually doesn't result in weight loss. But it transforms fat cells into muscle cells, which many people tend to prefer.
If that doesn't work either, investigating the viability of the drugs mentioned in the article above is an option. If you can afford them and they help, fine.
If you can't, or if they don't, then more drastic measures are required ... or you just give up.
Yeah
That's why these drugs work
So long as we are ignoring side effects, permanently eating zero calories makes you lose even more weight. Just a slight long term problem.
500kcal/day is actually a way to lose weight that's pretty successful in studies. You need those 500kcal/day to get enough proteine, which you can't really dispensed of during your diet.
But it's actually been studied that very low calorie diets tend to be more successful due to immediate and drastic effects, then healthier slower attempts at weightloss with only a slight caloric deficit. However, maintaining the weight afterwards is another story. You still need to adjust the life style to maintain that weight afterwards.
Why worry about something abstract like calories? Weight loss is a simple matter of Atoms In Atoms Out.
I kinda made the "Bob" method work for like 8 years. It was a little more complex than that though.
First step was a crash diet. 800 calories a day, ironically achieved through the use of fast food. I bought a single meal in that range, kept zero food in the house, doordash didn't exist then, and my roommate was under orders to take my keys if I tried to leave to get food. I did this for about 10 months. Lost 90 lbs. Ganked my gallbladder in the process and had to have it out. Turns out if it doesn't despense bile often enough, you get gallstones and hyperbilirubinemia.
Then step 2, after losing so much weight, exercise was wayyyyyy easier. Unimaginably so. I could run for 5 miles which felt being Goku, considering the rest of my sedentary life. Shin splints and ankle pains when running gone, fewer stitches in the side, and obviously more endurance, because less mass. I started eating like normal again, but exercise mostly kept the weight in check. I'd see-saw about 10lbs within a year, so high volatility and by no means thin, but I was not fat. (Side note: People really are so much friendlier to peiple with healthy weight)
Covid finally ended my spree, not being able to hit the gym, I gained weight, then got depressed which cause me to gain more weight. I'm still 30lbs down off my high water mark, but it's bad reversio . Overall, though I consider it qualified success. Even if I never lose back again, I probably extended my life by going for nearly a decade with healthy bp, triglycerides, etc.
I can't recommend my approach ultimately because there were lots of gastroenteric issues that cropped up because of it. Also, gotta be careful by adding vitamins. Crash dieting is correctly seen as unhealthy. I do wonder though, if this is something that GLP folks can take advantage of, coasting down to a "cruising weight" in the meds, then switching tactics to wean off the meds and eat normally while using aggressive cardio training. Bring the meds back when Covid 28 hits or whatever interrupter might happen that fractures the cycle. It might not work for everyone, but I suspect due to my experience, there's probably a significant amount of folks that don't have to take the ketracel-white forever.
Does anyone know how the ~$200 a month from compounding pharmacies compare to the raw materials? Is it sort of the price we'd expect from a generic version of the drugs? Without knowing anything at all about the manufacturing process, that seems like a high number to me if patents aren't coming into play.
I agree. Several people have claimed that the raw materials could be produced for pennies, though I don't know for sure that this is true. I think that everyone is buying from the same couple of factories that have some level of safety certification (although not as much as the real Novo Nordisk brand or any other normal drug does) and there aren't enough of those to drive down costs. But I agree this is mysterious, and it wouldn't surprise me if the people saying the raw materials are cheaper are wrong.
I know secondhand of a couple of people who have gone this route, and it came out to about $80 US per month at the dosages they were using. I imagine that the majority of that was shipping costs. Make of that what you will
Compounded tirzepatide from a licensed pharmacy is on average about 10x the price of peptides ordered from China. Something like $6/mg compounded vs .60/mg for the peptide. Who knows what the Chinese middlemen are paying but almost certainly a lot less less than .60/mg. So someone on the highest dose would pay like $360/month for the licensed compounding pharm version vs $36/month gray market. (Grey market has some extra expenses for other materials/group testing the peptides so call it $50/month.)
Your paying for the pharmacy, not just the drug.
Thank you, that's about as direct of an answer to my question as I could have hoped for.
Maybe I can collect my urine and recover the GLP-1 from it..
I read that's what they did with Penicillin at the beginning, when they didn't yet know how to produce lots for cheap.
> All of our patients just developed severe needle phobia, sorry, so they need semaglutide gummies.
I think this can be a legit loophole? Needles are scary after all and if it can be administered orally, much much more people will want the drug. Why haven't Novo Nordisk seizes this niche yet.
I think if the patient was previously willing to take the injection (which almost all current GLP-1 patients are), then by definition it's not "medically necessary" for them to have a non-injection formulation.
There's more info at the Recursive Adaptation post. My guess is Novo Nordisk hasn't seized it because they would have to go through a completely new FDA approval process for this "new" drug, it would be very expensive, and there isn't enough real-world demand for it. It's also possible that they tried, it didn't work, and they haven't told anyone because why make life easy for people who are trying to cheat you?
Yeah reading the RA article, conditional on gummies not being a good idea, I put 30% for FDA ban because it isn't "medically necessary", and 70% for it straight up doesn't work.
I wonder about how this relates to EpiPens—there’s a newish nasal inhaler version of epinephrine that the NYT wrote up with a lot of quotes from doctors whose anaphylactic patients were calling from the parking lot of the ER, etc, asking if they “really” needed to inject themselves.
EpiPens are about as medically necessary as medication gets, right? And yet fear of needles really can stop a patient from using the medication, even in a life threatening situation.
An intranasal formulation of a drug designed to counter airway blockage seems... risky.
They do have a pill version, though. It’s called Rybelsus. (Which you do mention in the post)
At least in some cases, companies avoid releasing new formulations because they're waiting seven years to do so. You see that a lot with sustained-release formulations; 3x daily becomes 2x daily becomes 1x daily, even though they could have easily made the better product from the outset.
That is true, but I hate needles and the ozempic injector is very easy for me - it's not painful and the needle is so fine I don't even feel it.
Getting blood drawn, on the other hand - oh gosh. Consistently a terrible experience, no matter how careful the nurse is.
I do think that would get more people to use vaccines. I do use them, but I would prefer not to have to get them via needles.
Pharma companies would not be successful suing doctors for writing scripts that don’t match their dosing. Maybe in a direct to consumer model of some sort, but when the pharmacy and doctor are financially separated
That aside, any company that charges more than 15% above the g7 average price for a medication should have their patent revoked unceremoniously.
I don't know, if I write a prescription/note saying that it is "medically necessary" for someone to get something, in a way that causes someone else to gain or lose money, I try to always do this in a way that will hold up in court. I don't think case this is that different from when doctors say it's "medically necessary" that someone get a surgery because they're secretly being bribed by the surgeon or something, and then lose their license for fraud.
I also think these telehealth companies are the kind of direct-to-consumer model you're thinking of.
I work in medicine. Lots of regular non tele-health providers use local compounding pharmacies to get patients glp1s. They aren’t attesting to anything being “medically necessary” when they write a script. They are just writing a script for available offered dosing. The onus for filling that drug legally is on the selling entity, the pharmacy. Again if you could prove some sort of illegal kickback scheme then sure, but otherwise you just won’t see this kind of lawsuit imo.
I am claiming that if there is a doctor who consistently writes 0.51 mg scripts, and when the pharmacy calls back and says "can we do 0.5 mg?" says "no, this is medically necessary", and has an employment relationship with a company that profits off of 0.51 mg scripts but not 0.5 mg scripts, and only ever seems GLP-1 patients for this company, then by the 1000th patient like this the regulators will notice a pattern and ask the doctor for documentation that the patient actually needs 0.51 mg, and when that documentation doesn't exist he will get in trouble.
But couldn't patients ask their non-shill GP to write them the "Mr Jones absolutely needs the 0.51 mg dose" prescription instead?
Shout out to Dean Baker who's been arguing against patents for years. EG here: https://cepr.net/publications/corruption-in-drug-patents-take-away-the-money/ and here: https://www.youtube.com/watch?v=cJJZUgt8kVM
As he puts it: "We need to understand the basic principle here. Patents are a government intervention in the free market, they impose a monopoly in a particular market."
This is from a liberal and relatively mainstream economist, pointing out the obvious weirdness of patents in our modern economy that's supposed to be based on free trade.
Sorry, strong disagree, see https://slatestarcodex.com/2016/09/07/reverse-voxsplaining-brand-name-drugs/
"Or maybe I am completely wrong about all of this. I am not an economist and have to take these studies at face value, and anything that touches pharmaceutical companies ends up being corrupted and full of lies. "
Maybe defer to the actual economist who wrote a book on the subject then?
I think the majority of economists, and especially economists who specialize in health care, take my side over yours.
Yup, Craig Garthwaite is my go to source on pharma pricing and innovation. This policy brief is pretty good overview of research in this area: https://www.economicstrategygroup.org/publication/why-drug-pricing-reform-is-complicated-a-primer-and-policy-guide-to-pharmaceutical-prices-in-the-us/
That's not how rational deference to expertise works. No one should defer to one economist when it's clear that the majority of economists disagree with that one (I'm not saying the one economist in this case is a quack, mind you; it's a legitimate minority opinion in the field.)
All well and good – but that's a reason for the state to cover prescription drugs, maybe even overpaying drug companies (they have a greater ability to pay than the average consumer), rather than a reason why individual consumers should pay high prices
https://www.pluralityofwords.com/p/misunderstanding-the-utilitarian
I agree that ending medical patents and replacing them with *nothing* might slow medical research in a way that's net bad.
But we could also do something else that is not that. Have the government buy out patents on actually useful new drugs, or have the government and charities set bounties on desired drugs that will enter the public domain once discovered, or have patents that do not grant full monopoly but do enforce royalty payments, or some other better policy that a subject-matter expert could probably think of.
Basically, I agree that we probably need to use money to incentivize research. But if society is going to spend $1B in order to invent a new drug, we can decide where that money comes form and what incentives it creates.
Right now, we are raising that $1B by creating artificial scarcity on important medications. While the pills themselves are cheap and could be made available to everyone who needs them for next to no cost, we instead restrict the supply so that lots of people can't get them at all, in order to create a high price point that pays back the research investment.
This has to be one of the stupidest possible ways of raising that $1B, because it's the only one that involves people *not getting the drug* after it's been invented and made cheap and easy to make. Buying out the patent with $1B in government money might not be the optimal solution, but at least then the government could make massive quantities on teh cheap and distribute it to everyone who wants it at cost.
I just read this and your old post on slatestarcodex. One question I don't see addressed is: what is the value to US consumers from pharmaceutical research being done in US? We pay a lot more for drugs here than the same drugs sold in other countries (acknowledging your point that generics, too, are more expensive than they need to be because of limited competition) -- does the consumer's subsidizing pharma research benefit consumers in the US to a greater extent than foreign consumers who pay less? I think maybe your response would be that if everyone behaved as the Europeans do by regulating/negotiating lower prices, then in the long run we'd have fewer new drugs and more deaths. (Not to put words in your mouth). But isn't it also possible that the savings to consumers that would result from regulation could be funneled to non-privately-conducted research -- and isn't it also the case that a lot of drug research happens at (sometimes) public research universities, so US consumers are actually subsidizing the research directly AND paying more on the basis that they need to cover research costs? And finally, I have read (sorry can't cite a source) that advertising budgets by pharma companies are far higher than research budgets, so isn't the pharma argument that "we pay more to encourage research" just a bit duplicitous?
If I recall right, Richard Posner has argued that the patent system in general is too favorable to inventors (e.g., because first-mover advantage is enough for tech like phones), but he made an exception for pharmaceuticals because the cost of invention is so damn high.
Is Posner assuming that all inventors are also skilled industrialists and salesmen? Because "first-mover advantage" doesn't count for much if you can't move, and you can't move into the market without manufacturing and sales.
Or is the idea that all invention is going to be done as work-for-hire for established industrial corporations?
Then what motivates invention? There's an upfront cost to be paid there and sometimes it's significant. What pays for that other than a temporary property right?
There's different methods. The method Dean Baker advocates for is that the government should offer prize money to anyone who makes an invention, rather than enforcing their monopoly. If that sounds too radical, we could simply decrease the length of time that patents are enforced. Novo Nordisk has had a near-monopoly on legal semiglutides for over 10 years now, and made hundreds of billions from it. Isn't that enough? It's simple enough for amateurs to manufacture in their garage, so all of their profits now are from government enforcing their monopoly.
A large portion of those profits are reinvested into drug discovery. If you reduce those profits you reduce the future availability of new medicines. There's a reasonable debate to be had there over where exactly to put that dial, but it seems a little silly to say that you're fine with patents if they're 5 years but if it's 10 then they're just "government intervention in the free market".
A government prize is just obviously wrong. That substitutes bureaucratic preferences for market incentives. How does that usually turn out?
Market incentives result in prioritizing treatments for chronic conditions that put people on drugs for life over one-time interventions or prevention. In general market incentives are supposed to work because people make more-or-less rational decisions, but health and the things that contribute to it are basically some of the hardest things for people to be rational about because they strongly trigger basic biological instincts.
Being less abstract about it, the US has some of the best healthcare interventions available in the world and spends more on healthcare than almost any other industrialized nation, and yet we're firmly mid when it comes to the actual health of our population. Not coincidentally, we're one of the nations that lets market incentives in healthcare run freest.
> A government prize is just obviously wrong. That substitutes bureaucratic preferences for market incentives.
Why would bureaucrats be the ones setting the prize quantities? There are *already* charitable foundations funding drug development (for e.g. malaria vaccines) on a "prize for success" basis. Making that the main system - replacing patents - could be a relatively simple matter of standardizing procedures, centralizing the 'bounty board' to reduce search costs or other needlessly duplicated effort, and acting as an escrow agency to make sure inventors and buyers both get what they fairly paid for. No need for such a program to have any particular official opinion on which drugs people are allowed to want, at least not beyond excluding uncontroversial egregious abuses like NBC weapons research, money laundering, or making dangerously addictive narcotics even worse.
Market incentives from patents reward rent-seeking, such as development of drugs which delay problems rather than solving them. Clean cure or easy prevention doesn't provide as much ongoing revenue stream. Managing that process creates additional operational overhead, and complex financial risks, which results in a "moat" restricting competition by new firms.
Lump-sum bounties would allow an R&D-specialized firm (even, in principle, some lone genius working out of his garage) to pay investors immediately and in full, hand over open-source plans to production specialists, close the book and move straight on to the next project, instead of being inexorably incentivized to make life harder for desperately ill people who *want to help test* those drugs by burying their best data in corporate counterespionage.
Billion-dollar prizes are going to be a huge political headache, with enormous pressure to cut down on the obvious "waste". They're also going to be much bigger litigation magnets than patents.
The economic models that are used to justify the patent system intellectually don't even model patents as such, rather they are obvious nonsense models that have the result that invention is maximized when the entire social benefit of an invention is internalized by the inventor specifically and therefore "something must be done" to make it possible for inventors to internalize social benefits of their inventions and "patents are something, therefore we must do patents".
The actual case for patents is basically status quo bias. What are the chances that the ideal economic mechanism for promoting invention was discovered by non-economists slightly tweaking a form of cronyistic government prize ("letters patent") used by kings in the mercantile age? Basically zero, yet here we are.
I don't know that it's that crazy to think kings in the mercantile age arrived at an efficient solution to the problem. If those kings went on to defeat other kings with worse solutions, then there would be selection for better solutions.
Creating monopolies was literally the go-to solution for everything in the mercantile age though, in most cases we got rid of it.
Will the lowest non-compounded price likely stay around $500 until the patent expires or might it decrease more? I assume if there are new competitors that come to market then it will definitely decrease in price, but if that doesn't happen I'm curious if time will be enough for the price to come down.
Good question.
If we assume that semaglutide and tirzepatide are perfect substitutes, then my very weak Economics 101 knowledge would suggest that they should compete each other down to the manufacturing cost, which is very cheap.
But in real life that hasn't happened, and it doesn't happen in other similar situations (eg generics with two manufacturers). Maybe a real economist can tell us why.
The basic econ 101 answer is that if there are only a few providers it is easy for them to collude to maintain monopolistic pricing. This “collusion” doesn’t even have to be negotiated; a tacit understanding that slashing prices by one of the providers will lead to retaliation by another is all that is needed. The more providers there are the more likely it is though that a “trade war” will start.
Yes, the search terms are "duopoly" for the special case of two providers and "oligopoly" for the more general case of a few providers. Pricing strategy in a duopoly or oligopoly scenario without explicitly agreed collusion is a form of iterated prisoner's dilemma: each firm can increase revenue in the short term by lowering prices, but if other firms also lower prices by similar amounts (either coincidentally or in retaliation), the total pool of revenue for the market segment goes down and each firm's share of revenue goes down. Any given firm makes more money (in the short term) if they lower prices, regardless of what others do, but everyone makes more money if nobody lowers prices. Optimal strategy depends on how likely other firms are to respond in kind if you lower prices and how likely they are to "defect" on their own.
There are a couple of added wrinkles in most real-world cases. One of the big ones is that production costs usually aren't all the same. If you know your firm can make, sell, and distribute the product substantially more cheaply than your competitors, then you may be able to "win" a price war by ending up in a position where you have a much larger market share, large enough to make up for the price cuts, while your competitor can't cut their own prices further without selling below marginal costs.
There are also sometimes ways to enforce a cartel indirectly by aligning incentives, such as cross-licensing: you agree to license patents to one another and make your products in such a way that each of you is selling something that depends on your competitor's patents. The license fees mean both of you profit any time either of you sells.
David Friedman has a whole chapter about this in his price theory text (Chapter 11 of the linked PDF), plus a few other considerations: threat of new firms entering the market, competition on factors other than price, price discrimination, most-favored customer clauses, etc.
http://www.daviddfriedman.com/Academic/Price_Theory/Price%20Theory-%20D.%20Friedman.pdf
If manufacturing capacity is limited, then there is no point in trying to compete on price, since you won't be able to take profits in higher volumes.
Yeah, there are a couple of more effective competitors likely coming to market in the next couple of years that should bring these two down in price.
There's always Canada! My doctor directed me to this site: https://overthebordermeds.com/weight-loss/
Last month I ordered a tirzepatide pen from them. The brands approved to treat diabetes (Ozempic, Mounjaro) are still sold in multi-use pens that you can portion out. The single-use vials with no preservatives are only for the weight loss brands (Wegovy, Zepbound). I wonder how Novo and Lilly will try to prevent everyone from just ordering the "diabetes" versions to stretch out the dose.
Including shipping and a new customer discount, it was ~$700 for what I will stretch out to 8 doses (so, ~$350/month). The package arrived with no Customs issues, but this was before all the tariff chaos, so who knows what the future holds.
Correction - it's only Eli Lilly that is selling Zepbound in the single-use vials. We'll see if Novo Nordisk follows suit for Wegovy.
>There's always Canada!
Let's hope so.
>Let's hope so.
Yup. :-/
> It seems unfair to charge these people twice as much for genetic bad luck.
This seems a strange ethical line for them to draw when the necessity of many drugs is up to genetic bad luck in the first place.
I agree! I'm just assuming their motivation here, maybe it's something else.
It's the same with pills. For many psych meds my patients take the cost of a high dose pill is very close to the cost of a low dose pill. So I advise the ones who are having trouble paying for their meds to buy the high dose and split the pills if. they're splitable.
I've always thought the reason high dose and low dose pills of a given psych med cost the same is that the amount of drug in a pill is a very small part of what it costs to produce the pill. The other costs, which are the same for high dose and low dose pills, are physically producing and packaging the pills, advertising, development of the drug, etc. Dunno whether that's true, though.
IIRC, during the early days of the opioid explosion, the rationale (according to some sources highly critical of the companies) was more “give them as much of this drug as they need/want/can tolerate for the same price as a lower dose” in order to sell more product. A little counterintuitive in the sense that more product could mean more pills, or more money, but the way they went was just more drug—in fewer pills, if necessary.
Sure, but if we look past that moral question, there's a pragmatic economic consideration that looks like:
Someone getting diagnosed with a condition, getting a prescription for that condition, getting the pills from a pharmacy, and getting all the paperwork and admin associated with that managed, is imposing a real and substantial cost on the system above someone with no condition and no meds.
But someone doing all of that and then getting the 10mg pill imposes almost no costs beyond someone doing all of that and getting the 5mg pill.
So if we want to claim that what people get charged is in some way related to what it costs to treat them, there's no justification for charging much more based on dosage.
>"So if we want to claim that what people get charged is in some way related to what it costs to treat them …"
That's not how pricing is done; people get charged based on the value of the product *to them*, which actually supports the dose-insensitive pricing: the value of a drug to a patient is related to how it improves their life, so they DGAF if it's 5mg or 10mg.
Maybe. But then you'd also charge rich people more.
Or at least you'd try to.
Drug companies do try to do this, by exploiting the classic time/money tradeoff by charging more for time-release or other more convenient formulations, or by selling me-too drugs that are incremental improvements at a higher price than the improvement really justifies.
A lot of businesses do try to. E.g. governments charge taxes proportional to income (or even progressively), cinemas give out senior discounts, and burger places charge €3 to add a piece of bacon to your burger. Price discrimination is ubiquitous.
I don't think I agree with your logic. If a medication I take is highly effective at 10 mg but only slightly improves my symptoms at 5 MG, I'd probably pay more for the higher dose if I had to, assuming that I could budget for it. I imagine other people would, too.
Or, if you need 10 mg to get blood marker x to stay at desired level y, 5 mg might keep your levels at dangerous level z. I'd pay more for 10 mg there if I had to, as well.
You're correct, but you're not disagreeing with my logic. :)
In your example, the 10 mg dose improves your life more than the 5 mg dose, so it's more valuable *to you*.
Someone who responds more strongly to the medication may see the same life improvement from the 5 mg dose as you do the 10 mg dose, and experience unacceptable side effects at the higher dose; they would value the 5 mg dose more than the 10 mg one.
The optimal pricing strategy has to account for the total demand curve; individual demand curves' idiosyncrasies largely cancel out.
There’s a layer beyond (beneath?) compounding pharmacies, which is people buying Semaglutide (et al) from research drug companies, and relying on trusted third-party labs. I haven’t scrolled through all the comments, but how does this ruling affect those outlets?
Can you point to any info on this route? Are you saying that I can pay a seller to mix the peptides for me, and there’s some kind of lab testing and/or reputation to give me confidence what I’m getting is real and safe?
I’d rather not discuss grey-market sources on an ACX thread (an abundance of caution) but Reddit is a wealth of information.
Scott talks about it and there is a link in the article. You mix yourself.
I saw that part - but want to hear more about “trusted third-party labs”. How is trust established? Are there vendors that will mix for me and give me a vial with preservatives? Are there third-party labs that can verify this? I understand why people don’t want to mention specific vendors, but it would be helpful to know how developed this market is and whether there are any best-practices.
Testing by independent labs--you send a sample vial from the lot of ten that you buy. No. Yes.
You gotta read, man. It's not something that can be explained in a comment. The link is there go dive in. It's fairly sketchy. (Not for me personally after reading pretty deeply about it, I stick with compound from a big pharmacy.) If you want mixed for you, trustworthy, regulated, etc. you want compounded, not grey market.
Reddit will point you to Telegram, where the discussion is. Lots of reviews of labs.
It doesn't; those come from China, they do not care about our rules.
I work at Ognomy Sleep, one of the companies listed on the Lilly Direct page (under Sleep Apnea), and at least in our case, they are partnering directly with telehealth startups with their own independent doctors (so not just pedaling the drug with their “Eli Lilly stooges”). In our case, we do have an objective to diagnose and treat sleep apnea beyond just prescribing tirzepatide, but that is now one of our therapy pathways. Can’t speak for the companies listed under Obesity or connecting with doctors through their other channels, though.
The mechanism doesn't require any collusion, you just only partner with doctors that are okay writing the prescriptions. If your partners stop writing prescriptions, you find different partners.
“For the past three years, ~2 million people have taken complex peptides provided direct-to-consumer by a less-regulated supply chain, with barely a fig leaf of medical oversight, and it went great. There were no more side effects than any other medication.”
I thought this wasn’t true? I had read several articles about a lot of side effects resulting from these compounding pharmacies for GLP1 specifically.
Yes, but what those articles fail to tell you is how many people on regular
drugstore versions of these drugs seek medical attention for gastric side effects, which are very common. And it is not rare for someone on one of these drugs to have such bad nausea or heartburn or constipation they are alarmed or just plain miserable enough to call their doctor or even go to the ER. I do not know whether the brand name drugs cause as many of these side effects as the compounded versions. but neither do the people writing these articles —
at least none that I have seen. Have you seen any that compare complications on brand name to complications on compounded?
I have tried both Ozempic and Mounjaro in compounded formulas. Both gave me brutal constipation and bloating that none of the various remedies/strategies could resolve. If you have GI issues, I would stay away from GLP-1 drugs in any form..
Well, but in the clinical trials 90+ percent of people on the trial drug hung in for the full year. Based on that and other things I’ve read it’s clear that most people find the side effects tolerable. You seem to be in the unlucky 10% who have intolerable side effects. By the way, I read that people on the lowest dose of Mounjaro, which I believe is 5 cc, lost weight about ¾ as fast as those on the high dose, and had far fewer side effects. If you haven’t tried low dose treatment, might be worth a try.
From what I can parse between the lines of the articles: (1) There is a genuine issue in that the compounded versions don't come in single-use vials, so the rate of dosage-related issues is higher. Everything else mentioned in the articles seems to be either (2) a simple recounting of the normal side effects of the medications, or (3) speculation that bad things might happen due to lack of agency-regulated testing. That last bit is presumably what Scott is talking about - despite the lack of agency-regulated testing, there don't seem to have been any reported cases of health problems caused by impurities.
The reason you need to read between the lines is that the drug companies and FDA like to wave their hands around rapidly to try to confuse the reader and/or journalist so they don't distinguish between (1), (2), and (3).
And for what it's worth: While it's clear that (1) is a real issue, it's abundantly clear that many people don't think that the reduced risk from measured vials is worth paying $750 a month for. We ought to consider whether those people may be underestimating or externalizing the risk, but we also ought to consider the possibility that they aren't, and that the tradeoff is worth it.
In general, injecting unclean things is more likely to cause infection than eating poorly prepared things, since your stomach acid does a pretty good job killing most bacteria in the things you eat. This makes (all else being equal) self-compounding and injecting more risky than self-cooking are eating.
It is not hard at all to draw up a specified amount into a syringe. But there are probably people
who are confused by the markings on the syringe, or
don’t how how to divide 10 by 4, or have the idea that taking more than the usual dose is a good idea.
FDA site on the subject infuriated me. They give the number
of people on compounded version who seek medical attention due to drug effects, but no data on how many people on the prescription version do so. I doubt that the number of the latter is small. One of the people I know taking the brand name version of the stuff ate a large meal and then spent hours vomiting so violently that she had sore muscles in her sides and back for several days after. Saw her MD, who said, yeah, Ozempic. can do that. FDA site is a lesson in how to obfuscate with statistics.
Yeah, but most meds have some side effects. In clinical trials of these drugs the fraction of subjects on the trial
drug who quit the trial was greater than the fraction of placebo subjects who did, but not unusually high for a drug trial. Can’t remember what it was, but I think somewhere between 5 and 10%.
> But this time if you do anything wrong, or are insufficiently clean, you can give yourself a horrible infection, or inactivate the drug, or accidentally take 100x too much of the drug and end up with negative weight and float up into the sky and be lost forever.
Anxious housewife over the moon at prospect of immortality.
Be the Chang'e you want to see in the world.
Ah, so *that* is why the jade rabbit is pounding medicine in the mortar!
If you think about it, the Incident with the Suns could have been resolved much more peaceably, if Ozempic syringes were used instead of arrows.
Just goes to show how short sighted myths are compared to sci fi tbqh
It seems to me that, if you can't recommend buying semaglutide from a Chinese/Indian manufacturer directly. You should instead not-recommend buying retatrutide from a Chinese/Indian manufacturer directly.
The only *real* risk is antibodies -- It seems that semaglutide results in GLP antibodies in ~2% of people over a <I can't remember> months timeline and tirzepatide causes it in <I can't remember>0% over a <similar amount of months> timeline.
retatrutide has no such studies, in my off-the-cuff experimentation local reactions to it seem stronger (bruising, gum swelling) *but* that's an n=1 using something like platelet hitting up an area more to ~= "this will reach your lymphatic nodes and get trained on to produce an antibody that has corss-activity to GLP-1" which is not super sciency.
Given that none of the drugs have good antibody data anyway, and the phase 2 for retatrutide is more than big and good enough to point to it resulting in more weight loss with essentially 0 side effects.
I would suggest people not-recommend that one instead.
More heart rate side effects than Sema/Tirz, no?
I only partially understand what you are saying here. Could you spell it out for us dummies?
There is a drug called retatrutide that is being developed by Eli Lilly as the next-generation version of tirzepatide (Mounjaro). It hits even more target receptors than tirzepatide, and phase 2 trials have shown it to be even more effective at weight loss. Phase 3 trials have not yet been completed, so it is not yet FDA-approved for medical use, and consequently not officially available in the US or Europe.
However, the same Chinese or Indian peptide manufacturers that will sell you semaglutide or tirzepatide will happily sell you retatrutide as well.
The rest of the post discusses the possibility of your body developing antibodies against these drugs, that might potentially cross-react with your own GLP-1. I'm not sure where OP got their data from, they didn't cite any sources, more realistically there is e.g. Mullins et al. (https://pubmed.ncbi.nlm.nih.gov/37700637/) which shows ~2% of tirzepatide-treated patients developing any sort of neutralizing antibody against tirzepatide activity, and <1% of patients developing antibodies that are cross-reactive against endogenous GLP-1.
Anecdotally, OP observes stronger injection-site reactions to retatrutide as compared to the others, and hypothesizes that this might correspond to a higher possibility of such antibodies developing. But they also mention that the link between these two phenomena is weak, which leads them to suggest retatrutide over semaglutide/tirzepatide when ordering from Chinese/Indian peptide suppliers anyway.
Thank you, I think I actually understood most of that . Progress!
Next stupid question: How/why would the body develop an anti-body to a drug?
For what it’s worth, I’ve been “microdosing” tirzepatide for about 2 months now—1mg/week, not for weight loss but for IBS-like stomach issues that have been so far untreatable.
4 weeks in, all my chronic gut issues resolved. That’s almost 10 years of IBS-D or “bile acid malabsorption” or whatever it was—just vanished over the course of four weeks.
How’d that happen? I can’t wait to read about it. In the mean time, I can’t believe my luck in finding a doctor who suggested trying this.
Wow, congratulations! That's wonderful. I hope it continues to work out for you
Hi Jean, this is the same for me. I may be able to help. My long-standing gastrointestinal issues were finally pinpointed as due to an extremely low production of pancreatic enzymes. I started Mounjaro for weight loss and my symptoms completely disappeared. It has been life-changing. Curious, I then found a study which showed that, totally incidentally, Mounjaro increases pancreatic enzyme production by 30% or so.
There are a couple of hacks Scott didn’t mention.
Since high dose and low dose injection pens cost the same, people are getting prescriptions for high dose pens then breaking them open and using a syringe to get several lower doses out of each. There are lots of how-to videos on YouTube.
Also, according to the NEJM https://www.nejm.org/doi/full/10.1056/NEJMoa2206038
lower doses are almost as effective as higher ones: Here’s percent of body weight lost in 72 weeks by Tirzepatide users by dose taken:
5 mg 15%
10 mg 19.5%
15 mg 20.9%(
So weight loss on 10 mg differs hardly at all from loss on 15 mg. And even 5 mg is not greatly different. Besides being cheaper (if you
hack injection pens), lower doses cause fewer side effects.
He did mention it, unless he edited the article recently?
> So usually they sell all doses at a similar price, opening an arbitrage opportunity: if they sell both 5 mg and 10 mg for $500/month, and you need 5 mg, then buy the 10 mg dose, take half of it at a time, stretch out your monthlong supply for two months, and get an effective cost of $250/month
Oh, yeah, I see that now. Not sure whether it was there all along. I guess the only info my comment adds is that even if you can only get the drug in a pen rather than a vial it's possible to open the pen and draw out part of the drug with a syringe.
You can also "dispense" the auto-injector pen straight into an empty sterile vial (readily available online), and then portion it out with syringes from there.
"Many people have to stay on GLP-1 drugs permanently or risk regaining their lost weight"
Can anyone explain why this is? My understanding is that all these drugs did was curb appetite. Do people just get insane food cravings again or something?
If their normal level of food cravings made them gain weight the first time, then it will probably make them gain weight the second time.
When I had a ~1-month lapse in my semaglutide supply, I was suddenly ravenously hungry and gained multiple pounds per week.
Gary Taubes suggests that „all these drugs do is curb appetite“ is wrong. Instead, they shift fuel partitioning away from fat storage (what low-carb diets also aim to do), which means more energy is available and appetite is reduced. Once a new equilibrium is reached, appetite returns even for people who stay on the drug. See here:
https://uncertaintyprinciples.substack.com/p/drugs-or-diet-2-lets-talk-mechanisms
That post just rejects the “set point” mechanism for no real reason (or, the author doesn’t understand it? It doesn’t even seem incompatible with their explanation!)
Parsimony? If I understand this correctly, people would have expected a decision to eat less to result in lower weight, which empirically it doesn‘t, so they arrived at the idea that the brain „defends a set point“, often too high. But why would the brain do that? If Taubes has a different explanation that does no longer need this dubious set-point mechanism then of course he would „reject“ it.
It would be worthwhile looking how pricing works. According to ACT the price of Wegovy in the US is $1000/dose. Here in Switzerland the cost is CHF 188 (US$213 at todays's exchange) - from the same drug companies supplying the US. (source: https://en.comparis.ch/krankenkassen/leistungen/abnehmspritze).
Suspect that’s the gross price ($1000)- the actual price once rebates etc are factored in is likely to be much less (but still considerably greater than in Switzerland).
Interesting article in NYT - free to read
https://www.nytimes.com/2025/03/14/health/wegovy-zepbound-cost-weight-loss-drugs.html?unlocked_article_code=1.304.jxVi.XTAt8GheVrSy&smid=url-share
Thanks. The challenge regarding many of these HE analyses lies with the validity of the assumptions that underpin the calculations. That and the absence of long-term data. Also, generics will be available in the next few years (at least for the first wave).
I’m sure you right about this. I once did CB analysis for large engineering projects and the results had to be perfectly in line with management goals. But that having been said, reductions in cost (say to Swiss levels) will ALWAYS give a better CB ratio. Basically with no downside for anyone.
Of course generics will also help, but at least in this part of the world (Switzerland) generics manufacturers carefully avoid any attempt to seriously disrupt traditional pharma (often they are offshoots of the old firms). And to make things worse we’re going to have to wait several years before the generics are available.
This is strange. I checked the site my pro bodybuilder friends use for the ever varying stacks they try and at $129/5mg of Semaglutide that’s $13 dollars a week (have no idea what bacteriostatic water costs) that’s a BigMac Meal.
I wonder how it compares to Clem 😵💫
Extremepeptides.com
Eroids.com is the consumer reports of street peptides - overseas suppliers for any conceivable substance
Another lists $79/5mg or $8 a week. Thats a lot less than $250 I suppose.
One of the things I’ve argued with about the “Big Get Rich” pharma model of trans is that test and estradiol are extremely cheap.
I noticed that Sustanon (mixture of different molecular weight Testosterones) was $55 for 3500mg (10ml) - at every two weeks that’s $550 a year - nobody is making $Billions off a handful of women masculinizing themselves.
Likewise estradiol tablets seem to be $15 for 30 tablets of 2mg, or $100 a year for men feminizing. Lifetime spend of $4000 or so.
It’s amazing how much this has grown since I first looked at it.
Bac water is cheap.
Then this is all a fascinating insight into phama pricing. Cheap cheap .
>I am not a lawyer but this is all stupid. What are the companies thinking?
I've been listening to the 5-4 podcast on the history of Supreme Court cases, and am coming to realize that 'this is incredibly stupid' is in no way a disqualifying trait for a legal argument to have. If the current judicial regime wants to side with you for political or ideological reasons, they are often willing to approve very stupid arguments to do it (or to ignore your argument and make up their own).
So they may well just be thinking 'throw up as many stupid arguments as possible, which will serve as ablative shielding in the courts as each one takes months or years to be officially legally struck down, and maybe one of them will make it to a sympathetic court that wants us to provide cheap medicine to people and sides with us despite our argument being stupid.'
Worse strategies have won out for major industries in the past.
I've got what probably amounts to a year's supply in the fridge from Hims. Maybe I'll go ahead and try to order from Ro or Henry under the wire to stock up.
But yeah broadly this has been awesome for those of us willing to dip our toes slightly outside the insurance/doctor system. It was fun while it lasted. I lost 50 pounds last year, basically effortlessly, from 220 down to 170. FWIW, I've found that once I'm acclimated to semaglutide, 1/2 or even 1/4 of the prescribed dose can keep me on the straight and narrow. Maybe helpful for anyone else pondering how to stretch their vials in the fridge, as our patent rumspringe comes to an end.
The list of things that might happen in twelve months reminded me of this joke from Thousand and One Night (...and maybe the king's horse will sing)
https://websites.umich.edu/~jlawler/aue/sig.html
It be like that sometimes.
> But this time if you do anything wrong, or are insufficiently clean, you can give yourself a horrible infection, or inactivate the drug, or accidentally take 100x too much of the drug and end up with negative weight and float up into the sky and be lost forever.
Presumably you only get a horrible infection if you inject it, rather than taking it orally? Although I guess inactivation or floating up to the sky are still issues.
I'm not actually in this market; I assume there's some strong reason why most people are injecting when oral administration is usually vastly preferable, but a quick Google suggests only that some people get more side effects. Perhaps I'm missing something
My understanding (nonexpert) is that all GLP-1 drugs require injection except for Rybelsus, a form of oral semaglutide where the manufacturers try to crank up the dose so high that you can get some even though it's got terrible stomach absorption. My understanding is that Rybelsus doesn't work as well for most people and causes more side effects.
In theory there could be a sublingual solution but that's the gummy idea mentioned earlier and so far nobody has gotten it to work.
One of the reasons Rybelsus causes more side effects is because it includes SNAC to "improve bioavailability", which seems to mean punching holes in the stomach or intestinal lining to allow the GLP-1 receptor agonist to get into the bloodstream. (Also, I don't know what happens if one injects a semaglutide+SNAC mixture but I'm not volunteering to try it.)
I’m not sure it works (haven’t tried it), but AgelessRX does offer a sublingual version
I know 'America medicine bad' is a stereotype at this point, but just to provide a reference point here in Australia:
- I have a monthly 5-15 min phone call with a doctor (actually a nurse-practitioner) who has been awesome at providing advice and talking through strategies for diet exercise etc.
- I pay A$350 for 5mg including overnight delivery (via a service called Evermed which seems to intermediate with whatever local pharmacy offers the lowest rate). That's about U$220 with current exchange rates.
- When I was on a 2.5mg dose my doctor actively suggested ordering the 5mg vials and dividing up the doses to halve the cost
- That price include *no* government subsidy of any kind - if there's a policy change it can basically only lower the out-of-pocket cost
- The monthly checkin appointments cost A$59 of which I get A$26 back via government Medicare bulk billing rebate
Something worth considering is what the situation would be like in Australia if the US were to adopt the same system.
Isn't all this patent skirting just eroding the incentive for pharma companies to develop new drugs? The market system can do a good job either supplying existing drugs or developing new ones but not both. It seems weird to celebrate just shifting on that trade-off. Theoretically the way to do a good job supplying existing drugs and developing new ones would involve non-market systems, which we're making no progress towards.
It hasn't been doing that so far because there's been a shortage and the pharma company literally hasn't had the drug to sell.
Now that the shortage is over, it would do that going forward, which is why the FDA is banning it. I support the ban on that basis, but think there are other things to celebrate about the compounding model. See last paragraph, "It’s no surprise that you can sell drugs cheap if you violate the patent. But it is interesting that the non-cost aspects work out so well. "
Fair enough. I might just be getting triggered by the term "free-market medicine", but I still think experiments in that direction will hit a dead-end.
For context, the cost of bringing a drug to market is ~$1.4Bn USD.
This includes basic research (itself not inexpensive) in a pharmacology lab, putting things in test tubes; checking they work in cells, then whole animals without catastrophic side effects; adequately purifying them (including with regard to chirality, see thalidomide), observation of all regulations during testing in humans (lawyers = £/$) plus the costs of running the drug trials themselves. Scientists and doctors don’t work for free, and neither should they. It all mounts up, financially.
Something like 90% of drugs fail to come to market: sometimes they simply don’t work as expected, or have un-ignorable adverse effects, or your Very Promising Drug is being tested in a few dozen human subjects and one of them dies (drives under a truck / is shot by the police / etc.) in which case everything is halted because to say the death is unrelated to the drug is inductive reasoning. (It might have affected judgement or behaviour, for example.) As most of the money will already have been spent by then, it’s for the successful drugs to recoup the outlay.
See also production costs, financing future drugs and keeping enough cash in reserve in case something bad does get through and a Very Large Number of people require compensation (see Ranitidine etc.). Also profit, of course. Patents, make-what-they-can pricing schemata and a seeming enthusiasm for treat-not-cure strategising do seem inevitable in this light. Compounding pharmacies and generics skip all of this.
Then again, without all of the above, I think it's unlikely we'd have the WHO model list of essential medicines. I’m not sure what practicable alternatives there are.
Disclaimer: I do not, and have never, worked for a pharmaceutical company.
I have no idea how the cost of bringing a drug to market is broken down and have no industry experience. When I went to look it up, I ran across https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2820562. It looks like most (~80%) of the cost of bringing a drug to market is marketing and sales.
I am left thinking that if the marketing and sales budget of a drug was a mere 100% of the R&D budget instead of 400%, and if GLP-1 agonists followed the same split as everything else, they'd cost $400/month and be very close to competitive with compounding pharmacies.
I may have missed something in the JAMA Network paper. How did you calculate the ~80%?
Marketing and sales: I live in the UK where pharmaceutical companies don't advertise directly to patients, and I'd forgotten this happens in the US. Perhaps this accounts for at least some of the disparity in final cost between the US and elsewhere in the world? I also wonder if the US market is effectively subsidising developing nations.
"When I went to look it up, I ran across .... It looks like most (~80%) of the cost of bringing a drug to market is marketing and sales."
I think you mis-read the paper.
The Key Points at the top says this:
"This economic evaluation study used data from public and proprietary sources to estimate the mean cost of developing a new drug from 2000 to 2018, which was $172.7 million (2018 dollars) but increased to $515.8 million when cost of failures was included and to $879.3 million when both drug development failure and capital costs were included. The ratio of R&D spending to total sales increased from 11.9% to 17.7% from 2008 to 2019."
So the drug companies spend about $900 million (on average) per drug that comes to market. And this is about 20% of the total sales per drug, so the average drug will cost $900 million to bring to market and result in $4.5 billion in sales.
How embarrassing! That's exactly what I did. That'll teach me to skim-read papers before bed.
Thanks for finding the problem.
A few years ago when I went on Liraglutide, they gave me a box full of pens and a box of needles. I set the dose myself on the pen.
This year I went on Semaglutide. The different dosages are different products. You get a single pen with 4 doses of a specific size in it. The active compound is diluted s.t. the pen is exactly used up. This comes packaged with exactly 4 needles.
I suppose this prescription technically allows me to buy just needles from the pharmacy as well. After all, one part of the injection process is to test the needle, and if it doesn't work properly it has to be discarded. But they're sure as hell making it as awkward as possible to mess around with dosages.
In general, I grudgingly tolerate price discrimination. But when physical reality makes it hard to do so and the pharma companies try to twist things around to do it anyway, I have zero sympathy.
I also grudgingly tolerate the need to get a prescription before buying a medication. But that mechanism should never be used for economic purposes; it should be purely about safety (and about triage/priorization in extreme cases).
There is also probably some safety advantage in making it hard to administer the wrong dose? Plenty of other injectable products, e.g. epinephrine autoinjectors, are sold in single-use packaging at a variety of doses.
Great idea. Lets totally dump the patent system for pharmaceuticals. It took Novo Nordisk over 30 years and billions of dollars to complete the FDA approval process for semaglutide (liraglutide was the first approximation).
https://www.acquired.fm/episodes/novo-nordisk-ozempic
https://www.acquired.fm/episodes/the-scientific-journey-behind-ozempic-with-lotte-bjerre-knudsen-novo-nordisks-chief-scientific-advisor
I am sure that without the patent and the extra profits from that, the next pharma looking for the next breakthrough will make that kind of investment out of the goodness of their hearts.</sarc>
I'm not recommending dumping the patent system! I specifically said the patent system was good! Read the post!
The patent system allows the patent holder control all details of the practice of the art. As long as the medicine is patented, compounding pharmacies have no ability to participate in distribution of the pharmaceutical. There is no first sale doctrine in patent law.
I just got back from a couple weeks in Mexico and you can buy most anything at the pharmacy. Wegovy is not a problem right now.
Did security or customs ask you anything about it?
No questions asked. The density of pharmacies in Puerto Vallarta is beyond imagination. It's really incredible.
Its OTC, or you had to bring an Rx from the States with you?
OTC
> They’re selling their medication in single-dose vials, deliberately without preservatives, so that you need to take the whole dose immediately as soon as you open the vial - the arbitrage won’t work!
Sorry if this is a dumb question, but, can I not still simply freeze the not-yet-used contents of the vial? Is freezing not effective at preserving the medication without the added preservatives?
I'm not an expert on this but I think repeated freeze-thaw cycles are bad for peptides. My guess is that it's fine in real life, but that enough people (including me) would be too nervous about theoretical risks we can't quite disprove to be willing to try.
I think you can get around this. If they give you a vial with enough active ingredient for 4 weeks, use 4 syringes to draw out 1/4 of the solution and freeze the syringes. Each week, unfreeze one and inject it. Then each molecule of peptide was only frozen and thawed once.
(1) The American healthcare system is insane.
(2) "They’re selling their medication in single-dose vials, deliberately without preservatives, so that you need to take the whole dose immediately as soon as you open the vial"
Ha! If people are desperate enough they'll just keep the drugs in the fridge and cross their fingers and risk that taking half the dose now and half the dose later will work out and not kill them.
(3) "There were no more side effects than any other medication. People who wanted to lose weight lost weight."
Well, I hope. I'm currently on the 1g/week dosage and haven't seen any major changes yet. I may have lost a tiny bit of weight, it does seem to be helping my blood sugar, but it's having a weird effect on my appetite - yes, I'm not eating as much at one meal. So hurrah, reduction in intake means reduction in calories means weight loss, right? Except that within 1-2 hours afterwards, I'm hungry again and so I end up eating the same amount, more or less, as before.
Or I'm snacking a lot - constantly grazing. No, now I won't eat a whole bag of crisps in one go - but I eat half a bag, then look for maybe a yoghurt as well, a handful of peanuts, some grapes, half a bar of chocolate, that kind of 'filling in the corners'. It's very odd. Before, I might eat the whole big bag of crisps, but that was enough (at the time). Now, I'm not eating the whole bag, but I'm grazing on several different things at the one time to make up for it.
Which are you on, semaglutide or tirzepatide? A 1mg dose is really small for either. I have done lots better on tirzepatide than I did on semaglutide. I'm at 7.5mg and am 2 pounds away from the blessed 25 BMI, the BMI that shuts medical professionals up when they want to blame your hangnails or hair loss or anything else on being overweight.
Semaglutide. I'm only ramping up because I re-started on the low dosage to get up to the 1g and see how I tolerate that.
The first time I was put on Ozempic and then couldn't get it because of the shortages, my doctor did switch me to Mounjaro (I think) but I couldn't tolerate it and had to come off. So now we're going slow and seeing if everything stays fine and then up to 2g if needed.
But the appetite thing is really weird. I'm getting none of the suppression or lack of cravings alleged, this odd "must constantly snack" all the time instead.
Seems like a good opportunity for someone to manufacture sterilized benzyl alcohol in sealed vials for addition to these unpreserved single-dose Zepbound vials. Hmm...
Does tirzepatide without preservatives *really* go bad immediately once opened? I'm not a doctor or pharmacist but it seems hard to see how the tiny pinhole opening in the vial (which is self-resealing once the needle's been removed) would make the drug become ineffective within a week unless there's a very strong reaction between the fluid and something in air. And there's zero awareness in the general public that the vials can't be opened and split -- I've never heard this mentioned anywhere other than here -- so if deterring people from doing that is the plan, Eli Lilly is doing a terrible job of it. My understanding is that the actual reason people aren't doing this is because until last month, Lilly Direct only sold the 2.5mg and 5mg vials, and only a very small percentage of users are on a dosage below 5mg.
If we’re talking about the versions from Eli Lilly (not compounding pharmacies) the method of injection is a single-use pen, kind of like an EpiPen where you push it down on the thigh and a needle springs out to dispense the dose for you. Unless you pulled the whole apparatus apart and extracted the medication, I’m not sure you could really get half a dose out now and half a dose out later.
You use the pen to inject the medicine into a sterile vial rather than your flesh. (Sterile vials with caps
can be bought online.)
When buying tirzepatide from Lilly Direct, Monjuaro is sold with an auto injector pen, Zepbound is sold in vials with standard insulin / subq syringes. I know pharmacies often sell Zep in auto injector pens but that’s not how Lilly Direct does it.
I looked up the patent expiry date for Ozempic, and it seems to be next year. Intuitively this doesn't pass the sniff test, but I could be wrong. Any one know of any information one way or the other?
https://www.ncbi.nlm.nih.gov/books/NBK602920/table/t03/
"Whilst the core patents expire in 2026, the secondary patents are set to expire as late as 2033." https://www.reddie.co.uk/2024/08/30/the-year-of-ozempic-an-ip-take/
Most obese individuals could save $200-$300/month just on food costs by using weight loss drugs. Add in savings on gas (MPG), shoe wear, medical visits, and even lower insurance (health/life) premiums—and the real cost is far less than $1,000/month. Plus, a healthier weight could increase income-earning potential. The financial equation might not be as bad as it seems. Thanks for the post!
Studies have found around 6–11% reductions in grocery budget, so unless your hypothetical obese individual is spending $35,000–$40,000 a year per person on food, I don't think you're going to see those kind of savings. Keep in mind the median personal income in the US is just over $40,000, and obese individuals are poorer on average.
Studies:
11% https://www.grocerydoppio.com/performance-scorecard/state-of-digital-grocery-performance-scorecard-h1-2024
6% https://www.fooddive.com/news/glp-1-drug-use-cuts-grocery-spending-by-6-study-finds/736313/
I was definitely skewing on the high side and included “food”, which includes eating out. It’s a combination of volume reduction of food, plus food category, ie eating more veggies $5/lb versis meat $10/lb.
I think many people, both obese
and not, are eating a lot of chips, sweetened cereal, cookies etc — you know, junk food carbs. And that stuff is *cheap.*. Switching from that to broccoli and salad makings is definitely going to make food costs go up even if calories are going down
Right. The cost analysis needs to consider reduced food consumption. Someone eating a $15-20 large pizza for dinner might consume only two slices after starting Ozempic - a significant reduction that offsets some medication costs.
The Walmart CEO has noted that GLP-1 users demonstrate lower caloric intake and reduced grocery spending, representing tangible economic savings.
Most importantly, the $1000/month creates an immediate cost framework for obesity that most people need, as we generally struggle to calculate the net present value of future health costs. For those needing to transform their health trajectory, this expense may be a reasonable investment compared to the long-term consequences of remaining obese.
I have long thought that moving away from a patent based incentive model in pharmaceuticals to a generous royalty based system that lasts longer (25 years?) may have advantages. Maybe not for every category of drug, but it is worth considering.
The penalty for patent infringement is a reasonable royalty
For some added flavor: the direct-to-consumer sales models Novo and Lilly are debuting are very legally dubious. It's illegal for a drug manufacturer to (1) pay healthcare providers to prescribe the manufacturers' drugs; and/or (2) pay patients to use particular healthcare providers. These models may do both, by (1) providing free marketing to providers (by channeling patients to them via the manufacturers' websites) in return for those providers acting as "stooges," as Scott puts it, and writing more prescriptions for the manufacturers' drugs; and (2) steering patients to specifically those stooge providers (again via the websites).
"end up with negative weight and float up into the sky and be lost forever." xD
Scott, there is one possible outcome you did not address. Organized crime. These chemicals are much easier and much safer to manufacture than the popular controlled substances distributed on our streets by narcotics traffickers. And the penalties for distributing these weight loss drugs is minimal compared to unlawful distribution of cocaine, meth, and fentynal. Although the weightloss class is not addictive in the traditional sense, those who are on these drugs do become desperate to get them when they are no longer available. Because little expertise is needed to manufacture them and they can be manufactured domestically, I believe organized crime is going to monopolize the industry. This is where the money is, and there is a lot of money to be made by those who can make these products at very little cost, are not regulated, and pay no taxes.
Organized crime spikes so many things with fentanyl these days who in their right mind is going to buy a weight loss drug from them?
But they do that because recreational drug users actually like taking fentanyl (to the extent that overdoses can cause a surge of buyers to the source that they know to be selling potent drugs).
Pretty much everyone "likes" taking fentanyl once they've had it a few times, which is why they are spiking other drugs with fentanyl to create new users rather than asking "would you like fentanyl with that?"
I had the same thought when this was last discussed: https://www.astralcodexten.com/p/the-compounding-loophole/comment/66361592. I called them "artisanal medicine suppliers from south of the border."
Economics question: if Novo Nordisk and Eli Lilly have competing GLP-1 drugs, why hasn't competitive pressure driven them to offer their respective product nearly as cheaply as the compounding pharmas? Can't be insurance if almost nobody's insurance covers it. So if NN and EL are competing with each other, AND the compounders, what accounts for the vast price difference? It can't be 5-10x more expensive to add bacteriostatic water the way the FDA would like you to, can it?
Someone asked the same question up thread with more in depth answers but TL:DR - competition between two parties is just called Iterative Prisoner's Dilemma, and we all know that there are non-defect strategies for that.
They're different products as well, though? So some people will do better on Ozempic/Wegovy, and some people will do better on Mounjaro/Zepbound due to different tolerance of side effects etc. The pie is big enough to carve up different slices of the market. If I'm losing weight on Ozempic, I don't need to go on the Eli Lilly product. Conversely, if the Novo Nordisk product is not helping, then I switch to Mounjaro. No reason to cut the prices of either to the bone since the potential numbers of customers is enough for them both to have half of the market each and still turn a tidy penny.
If it were the case that both products were equally effective and equally free of side effects, then yeah it would be worth competing on "our drug is cheaper". But as I said, some people won't be able to tolerate product A/B and so will have to try product B/A.
I love examples of Region Beta in the wild.
Great read.
These compounders are now doing to medication what the piratebay / megaupload was doing to movies and music: They are distributing something in violation of a license illegally.
I remember the ferocity with which the US government prosecuted Kim DotCom, it's interesting to see that the same reasoning is not applied here, or could Denmark have the owners of these companies extradited?
Megaupload caused $500m in damages, I would assume the lost revenue here is much larger.
I think Scott is wrong in his analysis of changes in formulation the compounding pharmacies introduced. The compounding quality Act makes this exception to the "do not make copies of marketed products" rule,
unless there is a
change that produces for an individual patient a clinical
difference, AS DETERMINED BY THE PRESCRIBING PRACTIONER,
between the compounded drug and the comparable approved drug." This, in essence, off-loads the problem to prescribing practitioners. And good luck to suing one of those multiple nurse practitioners who do the prescribing. This will take months, if not years
How were the telehealths able to sell the branded drugs (Ozempic, Wegovy, etc) at less than the list price?
I'm confused about the nature of pharmaceutical manufacturing. So one the one hand it's this incredibly expensive and resource intensive process such that it takes years for Novo Nordisk to scale up production to meet demand for these drugs, with prices remaining high the whole time... and yet apparently it's actually pretty cheap and easy for anybody to manufacture the same thing if we just don't block them from doing so via patent law? Couldn't Novo just license some of these other companies to manufacture the drugs in exchange for a cut of the profits rather than having to build up all of its own manufacturing infrastructure if that's the situation?
The incredibly expensive and resource intensive process is developing and testing the drugs in the first place. Especially the testing. Once you know with sufficient confidence that a specific arrangement of atoms will have the desired effect, producing that arrangement of atoms in vast quantities is *usually* pretty cheap.
But it typically costs a billion dollars or more to get to that point. Most of it "wasted" on failed attempts, but it's only by doing the expensive testing that you can ever know that.
The costs of development aren't really the issue, what I'm confused about is why Novo isn't able to ramp up its production quickly enough to supply demand now that that development process has completed, and yet these compounding pharmacies can apparently start producing tons of the drugs instantly.
Cant remember where I read it, but apparently the self-injecting pens were the bottle neck. Not manufacturing the pens, but setting up the sterile factory that put the semaglutide into the pens.
Novo could license these companies to sell their drugs into the US and European markets, but normally the FDA and its peers wouldn't license them as safe manufacturers without a substantial investment on their own part.
The implication being that the FDA has a lower safety standard for companies producing a drug during one of these official shortages, in addition to allowing them to manufacture drugs they don't hold the patents for?
The FDA isn't really in charge of enforcing the patents in the first place, although they might have a policy/regulation against devoting agency resources to verifying the safety of an unlicensed manufacturer AFAIK.
Really it seems like even under the declared shortage, the only thing that wasn't in at least a legal gray area here to begin with was the actual action of the compounding pharmacies measuring out the raw peptides and adding clean water and preservatives.
Scott, something I think you should investigate relative to weight loss and cardiovascular disease is a fructose- and sucrose-free diet. Doctors tend to steer patients towards low-fat and low-saturated-fat diets, but if you actually look at the literature, the evidence is way stronger that limiting fructose is good for your weight, cardiovascular health and levels of visceral fat, vs. a low-fat or low-saturated-fat diet. Yet for some reason the concept of a low-fructose/low-sucrose diet never seems to have reached patient recommendations or the public imagination. I've been trying it and I've already lost nearly 10kg, and feel better also.
BTW I tried ozempic but it made me very depressed and reduced my energy.
You really think a sugar-free diet hasn't entered the public consciousness?
Low carb has, but low-fructose not so much.
Interesting article in NYT (free to read)
https://www.nytimes.com/2025/03/14/health/wegovy-zepbound-cost-weight-loss-drugs.html?unlocked_article_code=1.304.jxVi.XTAt8GheVrSy&smid=url-share
Russian pharmaceutical company recently launched its own semaglutide with price per month from 30 USD to 80 USD (depending on the dosage).
O
What we've learned from the compounding pharmacy interlude is that these drugs should be administered with vial and syringe, similar to insulin, rather than with limited dosage range obtained with the commercial injector devices. They should often be started with lower doses and adjusted with much more flexible increments and intervals in accordance with the patient responses. This can be accomplished to some extent even with the commercial injection devices by mechanically adjusting the amounts delivered.
>turning amateur chemist and using Chinese peptides to make bootleg weight loss drugs
Breaking Flab