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Isn’t this phentermine? Wasn’t it part of the old phen-phen diet? One “phen” was found to cause heart problems.

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You said, “I have a pretty minimal insurance and it looks like if I got semaglutide my copay would be about $500/month until I reach my deductible.” I think you mean out of pocket limit, not deductible, though maybe your plan is odd. Usually, you get zero benefit until you hit the deductible.

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I tried semaglutide and it did nothing to slow rate of weight gain, just produced stomach upset, going up to 2.4mg injectable. I know one other person trying semaglutide and they reported something similar. I wonder if they played some clever games with their choice of patients. My expectation of how the news goes here is a whole lot of people who try semaglutide, maybe after fighting really hard to get on it, and find that it does nothing. That said, I know at least one friend of a friend, if not a friend per se, who claims that semaglutide was their miracle drug. So maybe still worth that hard fight, even if I'm guessing that the real proportion who get nothing out of it will prove to be over 50% in real populations.

Further fun fact: Semaglutide comes heavily recommended with diet and exercise and many stern injunctions about that! The actual insert sheet includes a graph for how much weight people lose with and without "lifestyle interventions" added. The two graphs are roughly the same.

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It’s quite disturbing how pills have become the answer to everything these days. The opioid crisis in rural America is a good example of what happens when pills are handed out like crazy. Nowadays any hyperactive kid is given what is essentially meth, anyone who is depressed is given SSRIs, etc. Big Pharma is swimming in money from America’s pill culture.

Edit: Okay, I’ll explain. You state that you hope semaglutide can be part of a transhumanist culture where all problems can be solved via taking pills. In this world, all of society’s ills can be solved via medication. We could also get rid of any disease, of anxiety, of depression, etc. Now, this does sound like a utopia… expect that it ensures that pharmaceutical companies will maintain an iron grip on society, like in Huxley’s Brave New World where Soma “solved” everyone’s problems. But we’ve seen from Big Pharma the failures of this method, most recently Purdue Pharmaceuticals being responsible for thousands of opioid overdoses a year. And you mention that semaglutide increases the chance of certain cancers. Who knows if there are more long-term side effects that may occur while taking it, just like with Oxycontin? That was supposed to be a miracle drug too, and look what happened.

Also, in a perfect transhumanist fully-automated-luxury-space-communism world, would obesity really exist? Everyone would have perfect GMO food engineered to be as delicious and nutritious as possible. No one would even be fat to begin with unless they want to be. In that case semaglutide would not be necessary at all.

Also, the promotion of semaglutide would divert attention from the current problems of food deserts. Instead of making sure communities have access to cheap and healthy food, it lets food companies put out as much junk as possible and hope the pill fixes everything. In addition, semaglutide would increase America's problem of instant gratification without facing the consequences, which many members of Red Tribe see as a problem (bootstrap theory/no holdouts ethos).

And then there's the whole other can of worms about transhumanism and designer babies and what it means to be human. But let's not even get into that.

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founding

I wanted to try semaglutide. My doctor was perfectly willing to prescribe it but my insurance wouldn't cover it and the out of pocket is steep. Ended up with phentermine which seems to be working well, we'll see how it goes. I'm curious why it's not prescribed, cheap and there's good evidence it works, although not as well as the new stuff.

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I couldn’t get Wegovy at a reasonable price when it was approved, and then Novo Nordisk started having huge supply chain problems with their injectors. Fortunately, Eli Lilly’s coupon for Mounjaro was less restrictive at first, though they’ve had to crack down as they have trouble meeting demand for both off-label weight loss use and for the approved T2D use.

I am what the doctors call “morbidly obese,” and it’s been more effective than anything else I’ve ever tried. Down about 35 lbs in the first three months, and unlike with other diets I’ve tried, I’m not feeling miserable or hungry all the time. Assuming there aren’t scary side-effects in the future, these really are miracle drugs.

I do expect the price to come down relatively quickly due to competition, which is a good thing.

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Are these drugs that have to be taken forever, or just for the duration while someone is trying to lose weight? And is there any data on whether, once weight is lost, there are recurring cycles where patients regain and have to go back on the drugs to lose again? I'm assuming those factors would be important in a long term cost model.

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Nov 24, 2022·edited Nov 24, 2022

Looking at the study on wegovy.com that I think your graph is ultimately derived from, " Both groups were instructed to take the medicine along with a reduced-calorie meal plan and increased physical activity. " Is this normal for this sort of study, do patients actually do it, does this reduce veracity of results?

On that note 7% of Wegovy takers left the study due to side effects while 3.1% of the placebo did, which is makes me somewhat skeptical that there won't be some side effects coming up in mass adoption. https://www.wegovy.com/FAQs/frequently-asked-questions.html ("How much weight have people lost")

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Neat, I was waiting for this post.

Btw a quick google search says it's "tirzepatide", not "tirzapatide"

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Check out Wegovy.com- like so many other expensive drugs the company themselves offer a copay card for pts with commercial insurance, to bring copay down to $15, no negotiation needed.

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'Eat vegetables' gets removed?

Wow

Just, Wow.

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I wonder how much the demand for Wegovy gets reduced by it being an injection rather than a convenient pill that you can swallow. Is there any chance it can be turned into a pill?

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In Brazil medications are in general very cheap, due to being completely on the open the market (you pay out of pocket, no insurance involved at all), there being a robust and we'll regulated generics market, and there being a lot of basic medications on public healthcare.

I just checked and Rybelsus is $80 for 30 3mg capsules (https://www.drogariaspacheco.com.br/rybelsus-3mg-novo-nordisk-30-comprimidos/p). That equals <$200 per year if I'm computing doses right (Wegovy standard dose is 2.4mg/week). That's $200 in Brazil vs $15k in the US. That's just crazy!

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Wegovy is not yet available in Australia but Ozempic has been widely used off label with anecdotally great results despite the dose difference. It costs only $130/month (no govt subsidy applies). Sadly due to supply issues it's now impossible to get.

We have liraglutide as our GLP-1 that is approved for weight loss. It costs almost $400 a month but a lot of people report success on lower doses (presumably trying to stretch the pens out a bit longer).

I haven't had a good look at any papers discussing dosing, but I do wonder how important it is to be hitting the higher doses that are recommended for the weight loss indication.

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Semaglutide and tirzepatide are both taken as weekly injections for weightloss correct? Could that also discourage people from taking it since a lot of folks don't like getting poked weekly with needles?

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> Until now, doctors didn’t really use medication to treat obesity; the drugs either didn’t work or had too many side effects.

Is it the drugs not working or just FUD about prescribing drugs off label?

The side effects and abuse risk for stimulants can't be THAT different than prescribing to a normal weight college student vs obese. Maybe a bit more concern for cardiac issues but minor I think.

Less controlled and weaker stimulants could also be used like Modafinal or Nicotine. Even a small calorie intake reduction could mean a large difference in total body weight over a few years.

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I think the amount of semaglutide being prescribed for weight loss is being undercounted in this post. I prescribe semaglutide regularly for weight loss but I have never once prescribed wegovy. It’s just way too hard to get approved. Instead I prescribe ozempic for impaired fasting glycemic or pre-diabetes (basically anyone with fasting blood glucose >100 or hgba1c >5.5) which seems to go through way easier. I don’t think the difference of 2mg vs 2.4mg is all that meaningful in terms of overall weight loss. Would be interesting to see what the real number is including these other diagnoses.

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as an interesting aside, Janssen's Invokana diabetics drug has also been proven to cause weight loss. https://www.fiercepharma.com/pharma/proof-concept-trial-j-j-s-invokana-combo-helps-non-diabetics-shed-significant-weight sadly the trials went nowhere after in 2017 invokana got slapped with a black box warning for heightened risk of big toe amputations. A risk that one may be willing to take to treat diabetes but not weight problems. There must be something in mechanism of action of diabetes drugs that causes this nice weight loss side effect.

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Never previously heard of any of these drugs.

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If it weren't so late, I'd try and do some back-of-the-envelope-math myself but how many fewer calories will Americans be eating if semaglutide is made widely available and works? Will the industries dependent on Americans eating calories put up any kind of fight to increased availability of a weight-loss drug?

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I wonder if semaglutide works best in those who overeat to begin with, rather than those who eat normally but have conditions that predisposes them to gaining weight, like Hashimoto's or PCOS, or genetically slow metabolism. If you gain weight on 2000 kcal/day, reducing your appetite might not do much.

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84% experience >5% weight loss and 66% experience >10% doesn't seem to me like it would make people's physical appearance change very much from how it is now, even if 100% of obese people can get the medicine. A 300-pound person who loses 10% of their weight is still 270 pounds. Am I not understanding some key part of this?

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Wait, how is NextMed is promising to get it for $138/month? That's less than half what you said it costs at a compounding pharmacy, and you already said that was inexplicably low.

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Do we have any estimate for the other medical treatment costs that are prevented by giving this $15k/yr treatment? Presumably heart disease goes down. What % of our healthcare spending is paying for emergency treatment for heart attack treatments in uninsured individuals?

I could believe this is one of those cases where prophylaxis is way more efficient than treating the later-stage / downstream health incidents -- although I wouldn't predict that we actually reduce medical spending (that would be too good a marketing claim for the companies to miss), this effect might substantially dampen the cost increase.

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Ok this gives me a chance to talk about my weird way of thinking about exercise and money.

Let's say that people genuinely would pay $15k per year for this drug if they had the money, but money is tight for them. This doesn't surprise me. People spend astonishing amounts of money on clothes, phones, cars, etc. to try to sexually attract people (in part) but this will almost always be less effective than moving from obese to healthy weight, regardless of how much you spend.

Ok, so, the way I think about this is that when I eat healthy and exercise, I am paying myself whatever I would otherwise pay to a drug company to achieve it.

So take the $15k. If doing 1 hour of hard exercise per day results in the same weight loss (which it totally would of course), then assuming a tax rate of 30%, that is the same as me earning $21.42k, paying $6.42k in tax (30%), and then paying the $15k to a pharma company.

So doing exercise earns me $21.42k/365 = $58.70 per hour before tax.

I bet a lot of the obese Americans would love side income of $58.70 per hour, work when you want, plus it'll significantly reduce your anxiety and depression, with no side effects other than positive ones...

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Canadian pharmacies charge about $300 per month for Ozempic.

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So . . . what are people's tricks for airline tickets?

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Laughed and giggled- had fun reading this while learning much.

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Nov 24, 2022·edited Nov 24, 2022

Practical update. I recently found that some varieties of Blue Cross Blue Shield insurance (through the federal employee program, at least) will now cover Wegovy (Ozempic) for weight loss, starting in January 2023. https://www.fepblue.org/open-season/whats-new-2023

Wegovy is on their formulary as a Tier 2 drug, meaning a copay of roughly $60/month.

https://www.caremark.com/portal/asset/z6500_drug_list807_OE.pdf

I don’t know how common this will be in the coming year, but it’s a start.

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I’m in Canada, and started Ozempic for wait loss 7 weeks ago, at my GP’s suggestion. Still only at 0.5 ml/week. (Diabetic dose is 1 ml, weight loss dose is 2 ml.) My doc says it would cost me about $300 a month once on the full dose, and likely wouldn’t be covered by insurance (yet). But my weight loss is steady, about a kilo a week since starting, and side effects are very manageable now. Because I’m still on a dose the insurance is used to, it’s covered. If the weight loss continues like this for a while, I will likely stay on just 1 ml, so as not to lose coverage.

My weight had crept up through middle age. About 7 years ago I had lost the recommended 10% of body weight, to improve cholesterol and sleep apnea. Did that quite easily by cutting out all sugar and refined grains (even fruit except the very occasional tangerine or grapefruit after supper). Maintenance of my lower weight wasn’t that hard, possibly because I’m quite active. Then COVID, work-from-home for a year and a half, everyone in the house cooking and baking up a storm, much less physical activity. All the weight came back, plus a couple of kilos, and I wasn’t managing to lose it again. Cholesterol back up, blood sugar creeping up, apnea worse, one knee starting to give me trouble, hormones getting out of whack because of excess estrogen storage (I’m post-menopausal)….

If these drugs continue to work as well as they seem to, the system will figure out it’s cheaper to pay for them and keep people’s weight down than to withhold them and pay to treat the consequences of the excess weight.

I wonder if how I feel on Ozempic is how naturally thin people feel all the time ; I get somewhat hungry, although it’s ignorable. I enjoy good food, but don’t crave sugar or junk food even when hungry. I eat a small amount and am satisfied, have no desire to continue. If I eat past that point (eating fast can take me there), I feel quite nauseous for a couple of hours.

So WHY is it that medications are so damned expensive in the US? I’ve never really understood.

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Asking the big questions: what percentage of people would actually want wings?

I think it depends a lot on the details.

- functional vs non-functional

- instead of arms vs in addition to arms

- do they smell? how long does your daily shower now take? Do you just shampoo them?

- expected impact on your sex life?

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Great post! I’ve done some research on this issue, so here are a few thoughts. I put relevant links at the bottom of the post to support my specific claims.

First, the low volume for semaglutide that you are observing is at least partially due to supply shortages. The drug has been in serious shortage for a while. Novo Nordisk also sells Saxenda (liraglutide) for weight loss. Over the last 2 quarters, Saxenda sales are up 59%, while Wegovy sales are down 18%. Saxenda is priced similarly, and Wegovy is a better product. So I suspect a lot of the Saxenda spending would be going towards Wegovy in the absence of the semaglutide supply shortage.

Second, spending on Wegovy might not fully capture use of semaglutide for weight loss, because some people might be taking Ozempic primarily for weight loss benefits. Ozempic sales are huge, and it is a top-20 spending drug in Medicare. After the clinical trial was published showing sustained weight loss benefits from semaglutide, Ozempic sales growth accelerated (though sales were already growing fast). Even though Ozempic is approved for the diabetes indication, it makes sense that people would take it for weight loss, because (1) there is a big overlap between the obese and diabetic population and (2) Ozempic is more likely to be covered by insurance.

Third, your estimates of the costs are somewhat exaggerated, because the drug manufacturer pays significant discounts to insurers. These discounts do not reduce cost-sharing, but they do reduce premiums. When thinking about the social cost of the drug, it's more accurate to think about the price net of discounts, as opposed to the list price. The Morgan Stanley report that you cited reports roughly a 30% typical discount from the list price.

Fourth, this is nitpicky, but when you say "almost 10% of all US drug spending," you are dividing a 2030 spending projection by what U.S. prescription drug spending was in ~2020. The Medicare actuaries project U.S. prescription drug spending in 2030 to be closer to 600 million, not 300 million. That's still a massive projection for spending in the obesity class. If you believe the Morgan Stanley projection, spending on the obesity class as a share of national health spending will be comparable to peak spending on the Hepatitis C drugs. The financial impact of the Hepatitis C drugs was a huge story. But this would be even bigger, because the Hepatitis C drugs were a cure, such that the spending surge was short-lived. Conversely, the obesity drugs are chronic medications, and we should probably expect volume to continue to increase post-2030.

Fifth, a remarkable thing about semaglutide that may have been under-emphasized in your post is the extent to which the weight loss benefits are being sustained. People who successfully lose weight tend to have a very difficult time keeping the weight off. To my knowledge, before semaglutide, the only intervention that had been demonstrated to sustain a >10% weight loss benefit for more than 1-year was bariatric surgery. So far, clinical trails are showing sustained weight loss benefits from semaglutide for at least 2-years.

Sixth, this post focuses on GLP-1 agonists, which makes sense, because those drugs are starting to have an impact today. But the Morgan Stanley report also notes that amylin analogue cagrilintide may be approved for weight loss as soon as 2025. This drug has a completely different mechanism than semaglutide, but likely offers similar weight loss benefits. The crazy thing is that the weight loss benefits stack. So Novo Nordisk hopes to sell Cagrisema, which combines amylin analogue cagrilintide with semaglutide, and hopes to offer a ~30% average weight loss. This is roughly double what semaglutide offers, and is getting closer to bariatric surgery efficacy.

Seventh, if Medicare decides to cover Wegovy, it would be relatively affordable for Medicare beneficiaries. Starting in 2025, out-of-pocket costs for prescription drugs will be capped at $2,000 for Medicare beneficiaries. And most Medicare enrollees with a 30+ BMI are probably already spending a lot on drugs. So at the end of the day, the marginal cost might be $100 per month or even less. And if you are near-poverty, you get cost-sharing subsidies, so the cost is only about $10 per month. Of course, this all depends on Congress changing the law such that Medicare can cover obesity drugs. Currently, there is a statutory exclusion that can only be changed through Congressional action.

That’s all I have for now. Here are some citations for various claims I made in this comment.

Semaglutide is currently in shortage.

https://www.ashp.org/drug-shortages/current-shortages/drug-shortage-detail.aspx?id=813&loginreturnUrl=SSOCheckOnly

Recent sales growth for Saxenda has been much faster than Wegovy.

https://www.novonordisk.com/content/dam/nncorp/global/en/investors/pdfs/financial-results/2022/Q3-2022-financial-workbook.xlsx

Ozempic was a top-20 drug in Medicare for 2020.

https://data.cms.gov/summary-statistics-on-use-and-payments/medicare-medicaid-spending-by-drug/medicare-part-d-spending-by-drug/data

For these obesity medications, manufacturers pay a 30% discount to insurers off the list price.

https://khn.org/wp-content/uploads/sites/2/2022/09/Morgan-Stanley_Unlocking-the-Obesity-Challenge.pdf

Prescription drug spending in the US in 2030 will be closer to 600 million than 300 million.

https://www.cms.gov/files/zip/nhe-historical-and-projections-data.zip

Context on the financial impact of Hepatitis C.

https://www.healthaffairs.org/doi/full/10.1377/hlthaff.2015.1194

The benefits of semaglutide are being sustained for two years.

https://www.nature.com/articles/s41591-022-02026-4

The Medicare out-of-pocket cap will be $2,000 in 2025.

https://www.kff.org/medicare/issue-brief/how-will-the-prescription-drug-provisions-in-the-inflation-reduction-act-affect-medicare-beneficiaries/

Background on cost-sharing subsidies for low-income Medicare enrollees.

https://www.cms.gov/files/document/lis-memo.pdf#page=3

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Another data point: was prescribed liraglutide in Switzerland. The cost is about $150 / month on the highest dose.

I lost roughly 8% of weight, then went off it due to gastrointestinal problems. It's very far from a miracle drug, feels pretty nasty. Have since gained back the weight (confounded with other medical issues, complete lack of exercise). I might try again with a lower dose.

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Serious though somewhat rude question - for people who don't go to the gym, why not and what would get you to go? It seems like for an individual doing an hour of cardio 3-4 days a week is a much lower hanging fruit than getting a prescription, dealing with insurance, remembering to take the medicine, and dealing with the side effects. I wonder if we're missing a similarly low-hanging fruit on a large scale by not subsidizing gym memberships or having state-run public gyms (this seems logistically way easier than solving the food desert problem). I've been fortunate enough to live within a short walking distance of a gym my whole life and although I'd probably still work out even if I had to drive/walk longer I probably wouldn't go as frequently as I do and might not have started in the first place.

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One point of data. I'm in Canada. My partner has been using Ozempic (that's what it says on the box) for weight loss for a few weeks. It was prescribed by their general practitioner. I have no idea what it costs because it's covered by our additional medical insurance.

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Re canada, if you are american and have a prescription you should be able to get semaglutides for a couple hundred dollars a month through CanShipMeds. (At least, you could as of a couple months ago).

Also, thanks for the shout-out! If I had known so many people were going to read that post I’d have probably edited it a bit more haha.

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Would the following conditions cause any updates on your predictions?

1. Humans are heavily influenced by celebrity endorsements.

2. Humans are motivated by perceived scarcity.

3. It's now an open secret that Hollywood, influencer, and tech celebrities are taking this.

4. There's shortages at certain doses already and supply is somewhat constrained.

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I'm late commenting but I don't see anyone mentioning metformin yet.

** THIS IS NOT MEDICAL ADVICE **

Metformin is off-patent and although its only on-label use is for diabetes, some people think it extends life expectancy. (The main evidence for this is that diabetics who take metformin live longer on average than people who aren't diabetic.)

Since I started taking it my blood sugar has dropped from the high end of the normal range to the low end, which I imagine is a good place for it to be. And I've lost a noticeable thought not dramatic amount of weight: maybe 5% or thereabouts, which moved me from "overweight" to the high end of normal.

Surely people who are thinking about taking semaglutide should try metformin first?

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Nov 24, 2022·edited Nov 24, 2022

Possible side effect: cures alcoholism.

https://twitter.com/bigjoshlevine/status/1550715749563613184

Particularly in interesting if this works by the same mechanism as the weight loss effects, which seems plausible. What other willpower weaknesses will be treatable by medication?

Would you take a drug that made you not want to cheat on your spouse? Would you want your spouse to?

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What about long term weight management with semaglutide? I’m under the impression that it can’t be taken long term and it’s unclear whether people regain the weight afterwards. Anyone researched this more extensively?

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Based on how Europeans react to discussions of obesity drugs, I expect that European healthcare systems will not cover it at large scale until it goes generic.

Maybe for BMI > 40 or something, they'll pay $200/mo; but obesity drugs are seen as vaguely immoral and if they cost a lot money over the short term (maybe it'll save a lot in the long-term, but if you're a health minister facing elections in 2 years, what do you prioritize, tackling obesity or the waiting lists that pregnant women face?), I don't see them being used at scale for a while.

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Nov 24, 2022·edited Nov 24, 2022

Is it just me or is a 30% chance obesity is cut in half by 2050 really low if you expect it to be reasonably cheaper by 2040 (66% chance its less than $100/month). Do you expect there to be other factors keeping people from getting it? Doctors still insisting on diet/exercise first on a large scale? As yet unseen side effects? Something else I'm missing?

Edit: or maybe its just what Neo says in his comment and a good number of obese people are more are more than 15% above obese for their height.

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To make an anecdotal point about accessibility and costs: my wife has been on ozempic for weight loss since 2021. She was never obese, but using the Alpha Medical telehealth service, she was able to get a prescription easily. The "visits" with her physician occurred on a monthly basis to evaluate her tolerance and progress with the drug, visits cost $30 out of pocket.

She's been on Medicaid (Medi-Cal in California), and ozempic is completely free for her. Her Medicaid eligibility recently came under review due to our marriage, so we'll see what happens there.

I'm not sure if her situation is unusual or an edge case of sorts, but ozempic has been quite literally miraculous for her. Low cost, unimaginably effective, and accessible.

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After a well reasoned article, the last line "US obesity half or less of current rate in 2050: 30%" seems to come out of nowhere. If Wegovy users on average lose only 15% of their weight, then even if 100% of obese people were using Wegovy by 2050, the obesity rate still wouldn't go down by half unless most obese people were <15% above the weight threshold that defines obesity, right?

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The side effects are real. In addition to my own experience, the Facebook and Reddit groups are full of people complaining about constipation and nausea. After a year, my side effects have let up. But initially I was carrying barf bags everywhere and chugging Miralax daily. Sorry if that's TMI, but if you're considering it, go in with your eyes open. Oh, and a couple of months of brutal fatigue, which mercifully resolved after 2 or 3 months.

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Pharmacist from The Netherlands. Price Ozempic is about 105 euro a month overhere. In about 2-5 years generic forms will be available, price will be than even lower. Furthermore: even more potent medicines and combinatioins are expected the comming years (average weight reduction about 20%?).

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Why does it cost $15,000 a year? That seems like a colossal amount of money for a drug.

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Me and my public sector GP colleagues in Finland do prescribe semaglutide (Ozempic) off-label for weight loss. It is not covered by the national insurance unless you have both BMI>30 and uncontrolled diabetes despite at least one ongoing antidiabetic medication. However, the cost of 115€/month(1) can be afforded by many. Lately the biggest issue has been the inadequate supply due to surging demand(2).

1) https://www.yliopistonapteekki.fi/ozempic-1-mg-injektioneste-esitaytetty-kyna-4-annosta-1-kpl-78173

2) https://yle-fi.translate.goog/a/3-12638874?_x_tr_sl=auto&_x_tr_tl=en&_x_tr_hl=fi&_x_tr_pto=wapp

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I look forward to a transhumanist future where obesity doesn't matter because the diseases associated with obesity aren't a problem.

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Semaglutide here in the UK is pretty easily available privately for £199 a month.

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In Finland, a relative of mine got Rybelsus prescribed to her for treating obesity (paying something in the order of 50e/month from her own pocket). For the record, she reports loss of appetite, but weight loss wasn't realized.

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I know nothing about weight loss, but if this really is a drug that makes you "feel full" then the pharma industry's gain should be the food industry's loss. I am not going to try to quantify anything but if tens of millions of Americans start eating less due to medication then that should have a noticeable effect on food consumption.

From the other perspective one could argue that it is a bit silly to spend big money to eat less when eating less is actually the economical alternative. In my experience stingy people, people who count their pennies, are almost never obese. For them it is simply more fun to save a dollar than to eat an extra dollar worth of food that they do not really need. It is probably no coincidence that the world's richest country, and the one that has been rich for longest, is also famous for its obesity. Penny-pinching might have had a better reputation if its role in keeping people slim was better known.

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This is the most I’ve enjoyed an article of yours since the taxometrics series in 2020-ish

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(Banned)
Nov 24, 2022·edited Nov 24, 2022

1. Scott writes: "I come at semaglutide from a transhumanist perspective. I want to hack genetics and biology until everyone is as tall as they want, as strong as they want, as smart as they want, and whatever gender they want. If you want wings, you should be able to have wings. And yes, part of this vision is everyone having the weight they want."

I'm not sure how this jives with either EA or a rationalist program. Maximizing the individual without aim cannot maximize the whole.

2. According to NYT, 11/22/22 "What Is Ozempic and Why Is It Getting So Much Attention?" $892 a month without insurance.

3. Wouldn't a large RCT really be the first step? There are side effects to this as is noted.

4. Obesity is obviously a significant problem. But I am ambivalent about the "disease ification". Eating less and exercise more seemed to work for a million years. Are there any other creatures with an obesity problems? Consider 11/21/22 NYTimes "Scientists Don’t Agree on What Causes Obesity, but They Know What Doesn’t", By Julia Belluz.

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The same drug in Brazil costs $ 500 / month and you don’t need a prescription (just go to the pharmacy and ask for it). So you could fly to Brazil ($2000) , buy the drug for you ($6000), someone else ($6000), go back to the US, sell the extra one for $15k. You got the medication for one year and made a profit of $1000 :)

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Can get it for a few hundred AUD per month in Australia as Ozempic. Well, you could, shortages now mean you can't.

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I'm in the UK and Ozempic is fully covered by the NHS (0 copay) for type 2 Diabetes patients.

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So who is ready for the headlines calling for these drugs to be banned because normal weight people are taking them to achieve the “starvation look” desired by models, resulting in anorexia style deaths?

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The economics of pharma is just so weird. I've been on injectable semaglutide for quite some time now (for diabetes), and my copay is $25/month. Apparently I haven't bankrupted my family's insurer yet.

As for the drug itself:

I've experienced none of the "oh, you'd immediately notice those" side effects, but I I hear that quite a few people do.

My A1C runs MUCH lower than it used to under any circumstances other than the one circumstance I couldn't sustain long-term -- lots of exercise that inevitably ended with terrible knee problems which brought the exercise to a long halt.

As for weight, mine used to bounce back and forth between 220 pounds and 250 pounds. Now it bounces back and forth between 210 and 220. I have dietary and exercise plans to get down to 200 soon, after which I'm hoping more aggressive exercise won't be as hard on my knees, which may lead to no longer needing semaglutide for diabetes OR weight control. I guess we'll see.

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I can't help but think that even in a country whose eating culture is as fundamentally messed up as the US, you could probably get a healthy, tasty, weight-loss-conducive diet for a lot less than 15000$ a year...

Also, what is it with diabetes that its medications turn out to be so beneficial? Metformin also has a reputation for helping with weight loss, plus reducing cardiovascular problems and maybe having general anti-aging properties.

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~€150 per month for Ozempic in Ireland. My doctor told me she was expecting shortages. She considers it a miracle drug for obesity, and also for older people with alzheimers/dementia because it keeps their blood sugar down which apparently has benefits for them.

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I've been prescribed Semaglutide for Type 2 diabetes for about six months now. It does seem to lead to earlier satiety, but I've not had any weight loss. Oh, and being in Scotland, the prescription is free.

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I'm not seeing any commentary for how well GPL-1 drugs work for those that have a disconnect between hunger cues and eating, like anorexics turned binge eaters and all the people who could be classified as disordered eaters. I can easily see how drugs like this would work well for someone who always feels actual hunger pangs, so I think my question is, how well does it work for someone who doesn't/has never associated eating with anything other than as a reward or a drug in and of itself? Who couldn't tell you what "feeling hungry" even means? The idea that a drug would make a person feel full or not hungry and therefore not eat ... I can't even envision what that means thanks to said disordered eating.

I do have experience with taking phentermine. It helped calm my mind and by escaping that noise helped improve my overall attitude, but I was still quite capable of gaining weight while taking it.

In such circumstances, does anyone have experience or thoughts with how well GPL-1 drugs would work for weight loss/maintenance?

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Personally, I've gone from about 185 to about 140 with moderate restriction of carbs, but I know people vary so much that nothing works for everyone, and most weight loss methods aren't a stable solution at all.

Part of my situation is that I actually like high-fat/high protein, though I don't like going without carbs completely.

I believe the culture is all too cavalier about the quality of life-- and the lives-- of fat people. Considering the extent to which the income and romantic possibilities for fat people are limited, not to mention the general lack of respect I wonder how much of the health effects (not all of them, but a fair amount) can be explained that way.

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Nov 24, 2022·edited Nov 24, 2022

Ozempic is available in Germany, 3 Pens (0.5mg each) cost around ~240€ so 80€ per 0.5mg.

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Nov 24, 2022·edited Nov 24, 2022

I wonder about the adoption of the medication, though. I took victoza (=saxenda, but approved for diabetes) and the absence of the desire to eat lead to some unforeseen lifestyle side effects. Given that 5 almonds made me full for the day, I was not interested in having dinner with the family or going out with friends. There is the reality that some restaurants would probably not be happy if you only ordered the smallest appetizer. In addition, alcohol was also very difficult, because the drug slows down gastric emptying and your stomach ends up absorbing alcohol for hours. I got really, really drunk for an entire night from a single glass of wine once. Before taking this drug I had not fully appreciated how much of one's (social) life revolves around food; lunch break with colleagues, dinner with family or friends, drinks on the weekend, a sweet treat, snacks and a movie etc. But once I was not interested in food anymore, combined with the tiredness that comes with eating little, a lot of those activities also lost their appeal. (On the upside, I slept like a log.)

Given that obese people's lives likely revolve a lot around food, its selection and its enjoyment, halting that activity so drastically may not be all that desirable for this population from a quality of life perspective.

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I am a pharmacist from The Netherlands. Price for Ozempic here is about 105 euro a month. In 2-5 years I will expect generic forms that willbe much cheaper. Furthermore I expect newer and better medicines and combinations (about 20% weigh reduction?). These products are a gamechanger for diabetic treatment and weight treatment. However the weight reduction is somtimes so quick and intense that I have a feeling that this is somtimes to intense and not healthy.

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Nov 24, 2022·edited Nov 24, 2022

It seems to me that America basically has a tiny communist microstate consisting of health care, plus insurance and academia.

Prices have basically nothing to do with supply and demand of goods produced in competitive markets, and are instead set, more or less, through central planning. Bureaucrats decide where to allocate research dollars, how much medical procedures cost, what insurance must cover, etc.

It's not _totally_ communist, because you do have different business competing, but it feels like it's maybe ... 70% of the way there.

The thing that perplexes me here is that basically everyone seems to do it the same way. That 'health care systems different from ours' post makes it clear that there really isn't anyone treating health care for humans the way we do it for, say, animals, or cosmetic surgery where price signals reflect supply and demand, insurance doesn't cover anything, and as a result things are cheaper.

Why is that? How come there isn't a single state doing something 'free market' with health care?

The best answer i have says something like, 'if the capacity exists to save a dying person, and it doesn't get used, people will rebel against whatever political status quo prevents that capacity from being used, even in autoritarian situations'. If the capacity does exist, and it _can_ be used in theory, but in practice you can't because it's too slow an ineffective, people are less likely to rebel.

So it seems like, 'constraints must be illegible in order to survive popular wrath'. You can have much, much tighter constraints than 'you can't afford this so you can't use it', and people will generally accept them so long as they involve 'safety regulation' and 'labor shortages', etc. A cartel that restricts the number of doctors is totally politically feasible, in a way that 'this machine could save your child but you cannot afford its use' is not, even if the cartel restricting doctors is way, way way more destructive.

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I would guess that adding obesity related conditions would help with getting insurance to cover it, and this may play a role with how startups are getting insurance coverage: eg, hypertension, sleep apnea, etc.

As long as there is no fraud that seems ok.

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Here's my Ozempic story: So I wanted to get pregnant and had been trying 'the old-fashioned way' for a year. My fertility doctor says I have to lose weight for fertility treatment. In a panic I rush over to my endocrinologist who says 'let's put you on this Ozempic stuff so you can get Clomid.' Okay great. Two weeks in and I'm down 10 lbs. I have to take a pregnancy test before each injection. Okay, about to do infection #3...take my test...and I'm pregnant!! For the next 9 months, I keep hearing jokes about how Ozempic must be a fertility drug....your AMH was WAY too low to get pregnant, etc. Okay, October 2021, I have a beautiful, healthy baby girl. Endocrinologist says I can start my injections as soon as baby's calories are at least 50% from solid food or formula, 50% breastmilk. Okay, okay. I just need to wait and be patient. Well, joke's on me, and my baby girl won't eat and won't drink anything other than breastmilk. She's 12 months old, and in OT to teach her how to chew. And it will be almost 2 years that I will have had 6 months of Ozempic sitting in my fridge. Is it expired? Do I try to sell it?! I don't know...

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This article is really useful especially today.

I have a theory about obesity. The mention of the “family” factors — small group - is on the right track. Some people have a condition where they themselves are not overweight but they obsess about the weight of those in their immediate circle. We arrived at the home of this relative last night. This person complains significantly about others’ weight behind their backs. For some reason they had a large tin of cookies & immediately made sure we took it with us to where we were staying (this was not a planned gift). They’re almost a type of poisoner. I resisted the cookies but dang. Someone who hangs around undermining the willpower of others is a common character in the US I think, maybe everywhere, I just happen to be related to this one. Seventy percent odds this person mentions Wegovy before today’s large meal. 99% mentions within 48 hrs. Finding and somehow intervening with the people playing these roles would lead to improved weight control among those in their circles.

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Your estimate of the proportion of annual healthcare expenses going toward semaglutide in a world without barriers to usage assumes that the obesity rate (or population of obese Americans) stays fixed. If this drug works, there'd be a significant one-time expense and then, presumably, minimal expenses to follow (unless the drug were required for weight maintenance in the formerly obese). Not to mention the knock-on effects of lower expenses for obesity-related disease. As an extreme example, imagine a one-time 50k pill that prevented you from ever getting sick again - I couldn't care less about the proportion of annual spending going toward that drug the first year it was released.

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Good article about the drug, the annoying thing is the use of BMI.

It's a bad measure.

1. It's not dimensionless even though people use it like it is. Metric BMI vs. Imperial BMI are not the same number.

2. The (admittedly small) minority of people who have more muscle are unjustly persecuted by their doctors for being "obese".

I admit self-interest here. My (Imperial) BMI is 35, I'm able to deadlift at least 3 times what my doctor does, but I'm the obese one who needs to go on a diet. I did shut him up about it by pointing out that even the US Navy has stopped using it as a measure for their incoming recruits (IIRC they use height/weight/waist/neck plus a chart now - I guess they had too many people able to lift a car but they can't run so they can't be on a ship until they lose weight).

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IIRC Calibrate's pitch to insurers is that by pairing Semaglutide with their behaviour change program (app + coaches) they can eventually wean people off the medication while maintaining the weight loss effects, saving insurers lots of $$ in the long term. So far they've been quite successful convincing insurers (and VCs) of this but I think the evidence shows people need to stay on Semaglutide forever to maintain their weight so I don't think this will hold up.

I would be surprised if Semaglutide was cheaply available as a generic by the mid-2030s unless there are significant reforms made to the patent system or pharma industry rules. Humira and Lantus are good examples of drugs which would be significantly cheaper by now except for repeated patent extension and industry deals maintaining monopolies (although hopefully coming down soon).

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Surely eating less can be translated into paying less for food,, offsetting some of the cost of the drug.

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I have a condition that the NHS doesn't really have a good way of treating (eczema), except for an American drug, called "dupixent" or "dupilumab", that they're extremely reluctant to prescribe because of the cost (about 40k annually).

Should I expect a much more affordable generic, or the cost to go way down, when the patent runs out?

Maybe someone here has some insight, I really would like to know. Apparently it's a type of drug called "biologicals", which are expensive to produce, so maybe even at production cost it would still be prohibitively costly, but surely not 40k costly.

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As soon as I saw "$500 billion" I thought "That doesn't sound like that much money if it really is a miracle drug." And I think the research about the monetary breakeven point neglects a lot of other potential good side effects. For example, this link from 2012 suggests that Americans waste one billion gallons of gas due to being overweight: https://www.forbes.com/sites/matthewdepaula/2012/10/09/american-obesity-the-biggest-threat-to-fuel-economy/?sh=4acd77c65e92

The same thing applies to overweight people on airplanes. And trains and buses, for that matter.

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One thing about the idea of a post-obesity future: if the average responder can reasonably expect to lose 10% of body weight on Semaglutide, that would still leave most of them obese.

AFAIK the standard categorization for 'obese' starts at 30 bmi. Rough napkin math with a BMI calculator makes me think that anyone who starts at about 30-33.5 bmi and then loses 10% of body weight will end up below 30 bmi, but anyone who starts out above ~33.5 and loses 10% will still be obese.

5 minutes of google didn't find me a precise answer to 'what percent of the US population is above '33.5bmi', but it did find some distribution graphs that makes me roughly guess it would still be like 25%-35%.

But maybe the 10% figure comes from a 3-month clinical trial, and if you take it for 5 years you just keep losing until you are at a 'healthy' weight? Or maybe you gain tolerance over 5 years and end up back at your original weight? Seems like a lot is left to be learned about those dynamics.

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My father is Canadian, and I was talking about weight loss with him a couple of weeks ago, and he says he has semaglutide. But he doesn't take it because he feels it would be cheating to lose weight that way.

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I came to make the "using a pill to fix all our problems sounds terrible" post. I see others have made the same point above. To take a step back, this feels like more of a me-midlife-crisis problem than a problem with Scott's analyses or arguments.

There are two things recently that have made me think "the modern world is terrible." The first is Britain's new and ongoing reliance on food banks. A rich country in which a significant number of people can't get enough to eat: that's gotta be a sign that something is messed up.

The second is this: rich and resourceful societies around the world that can't get a grip on the deliberate infliction of chronic disease on its citizens by themselves/corporations/society, and instead turn to a pill to solve the problem.

These problems aren't turning me into a conservative, as is often supposed to happen, but they are for the first time ever making me think, at the age of 41, that the world is going to hell in a handbasket. I apply a very low level of credence to this belief, because it's overwhelmingly likely that I'm just thinking it because I'm middle aged. But I definitely do think it now.

In both these cases, it feels like building the right kind of institutions could prevent these things from happening; but something is preventing us from building those institutions. I can't work out what's going wrong. I mean, bloody Tories or whatever, but I don't know if it's really a party political problem.

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Would it be 2 of 3 (kind, true and necessary) to ask if Scott owns any stock in the companies making the stuff?

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> I model semaglutide use as interest * awareness * prescription accessibility * affordability.

You are multiplying quantities that are uncertain and the product of multiple distributions is better modeled as a log-normal distribution (and I guess some of your inputs are also already log-normally distributed). And for a product of such quantities the mode is left of the mean by more than one std dev. Did you take that effect into account when estimating the individual numbers?

https://en.wikipedia.org/wiki/Log-normal_distribution

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I friend of mine is on Contrave, and has lost *lots* of weight. I tried two of her pills, and somehow forgot to eat most of both days!

She got them through a "fly-by-night telemedicine company" and pays $600/month. The pills themselves cost ~$100/month, and $40 if you get the components separately.

Are there more reasonably priced telemedicine places? I fully expect tons of hidden fees on top of their advertised rates...

I suspect my regular doctors would get me on diet & exercise, which I'm already failing at. But maybe I should give them a try before I go Gray Market?

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For what it's worth, Scott, though people may feel it isn't worth the risk due to not exactly being legal, it is fairly trivial to get semaglutide from a grey market lab that just buys bulk chemicals from Chinese raw suppliers to package and resell in western countries. At the one supplier I know for sure is selling tested, real stuff I've seen other people use and get results from, it's currently $120 for a two-month supply. But many, if not most, sellers of research peptides will stock this. You can even get reasonably-priced HGH if you want a little extra lipolysis kick, and in spite of the scare stories from moralizing legislators trying to make examples of pro athletes for cheating, it is extremely safe if you're not doing bodybuilder-level doses. Yet another thing anyone over the age of 40 can get a prescription for by going to any anti-aging clinic, but they're going to charge through the roof and your insurance will definitely not cover it.

Feel free to cry for pharma companies losing some fraction of their precious patent-protected dollars, but $15,000 is utterly absurd. There is no need at all to pay that much.

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"PCP" means "personal care physician" in the context that Scott is using it. I only bring it up because the expansion of the acronym wasn't obvious to me and googling it isn't helpful.

"Only 75% of Americans have PCPs at all." Just curious if am I the only one who got confused by this?

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Ugh. I’ve been wanting to take Wegovy ever since I heard of it after Elon Musk’s tweet, then went down a rabbit hole on it. Sounds waaaaay safer than Phentermine, which they give out like cheap candy and is terrible for you, plus doesn’t work for many because of the side effects.

I hope they can reduce the Wegovy price. I can’t justify the payments.

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"(there’s also a third-level effect where it costs the health system money again, because it prevents people from dying of obesity-related complications, and dead people stop needing expensive health care. I think health economists are supposed to ignore this level.)"

I am regularly pretty frustrated by arguments that ignore this level, because if we're going to have a discussion specifically on economic grounds, it seems like a glaring omission. There are many versions of "Spend money to prevent this person from dying, because people use a lot of resources when they die, so costs will actually go down." You can still make the argument on moral grounds, but don't use an economic argument that assumes that near-future people will be immortal.

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[Epistemic status: tongue only 33% in cheek]

Obesity should be renamed to crappyprocessedfoodoholism, to highlight the fact that you can avoid it by eliminating all the crappy processed food from the environments where you eat. Obesity was almost nonexistent before we got an industrialized supply of highly refined carbohydrates and oils combined into superstimuli. If you eliminate all the liquid/powdered calories and deriviatives thereof from your food supply, it's really hard to get fat. OTOH 97% of the calories in the supermarket consist of that kind of crap, so it's hard. People don't want to be thin as much as they want to eat processed crap, and there's a lot of bad information out there that derives from rationalizations thereof.

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I have been taking Wegovy for 14 months. When I began I weighed 275 lbs and my BMI was 39.9. I have hypertension, albeit well controlled by medicines. Diet and exercise phaaahhh. I could eat faster than I could exercise. And no, I eat very little fast food and little candy and soda.

I worked with my doctor to be prescribed Wegovy. It was only approved by the FDA in June 2021. My doctor was reluctant because he was unfamiliar with the class of compounds. He does not like to prescribe off label so he was not willing to to start me on Ozempic. But, the FDA solved that problem.

I knew to ask for the drug because my daughter was pre-diabetic and had been put on Metformin and Ozempic. She lost 100 lbs. in 2019 and 2020.

I started on Wegovy in September 2021. I now weigh 220 and my BMI is 31.5. That represents a 20% reduction in my original weight. 220 was my original goal. To get a BMI under 30 I would have to be under 209. I doubt that I will get there. I am back in 40 in. trousers which I had not been able to wear in 30 years. 220 was my original goal.

I have had no major side effects other than constipation. Even that is a little hard to tease out. I am on 7 Rx drugs and at least 5 of them are constipating. I have been pounding Metamucil and Colace for years.

I have been able to fill my prescriptions using a GoodRx coupon at $1328 for a box with 4 injectors. A year requires 13 boxes. The total cost for 15 boxes has been about $20,000.

I can afford it and it has been worth while. I call it a bargain, the best I've ever had. https://www.youtube.com/watch?v=v6O5slQFFhc

I understand that it still way too expensive for the American health care system to afford. But given the bonanza size of the market. There will be lots of competition starting with the Lilly's tirzepatide. There are several other pharma's with GLP-1 agonists in development. I am sure that the cost will come down.

My doctor tells me that I can expect to stay on semaglutide for the long term. He is proposing that I switch to Ozempic 2 mg for maintenance as I can buy that for less than $1,000 for a four dose pen.

My only sadness is that semaglutide wasn't invented 40 years ago when i would have saved me from a lot of damage. But, I am grateful that it exists now and that it has helped my daughter so much.

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"Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial"

| Garvey ae.t.al. and the STEP 5 Study Group*

https://doi.org/10.1038/s41591-022-02026-4

"The STEP 5 trial assessed the efficacy and safety of once-weekly subcutaneous semaglutide 2.4 mg versus placebo (both plus behavioral intervention) for long-term treatment of adults with obesity, or overweight with at least one weight-related comorbidity, without diabetes. The co-primary endpoints were the percentage change in body weight and achievement of weight loss of >=5% at week 104. Efficacy was assessed among all randomized participants regardless of treatment discontinuation or rescue intervention. From 5 October 2018 to 1 February 2019, 304 participants were randomly assigned to semaglutide 2.4 mg (n=152) or placebo (n=152), 92.8% of whom completed the trial (attended the end-of-trial safety visit). Most participants were female (236 (77.6%)) and white (283 (93.1%)), with a mean (s.d.) age of 47.3 (11.0)years, body mass index of 38.5 (6.9) kg/m–2 and weight of 106.0 (22.0) kg. The mean change in body weight from baseline to week 104 was 15.2% in the semaglutide group (n=152) versus 2.6% with placebo (n=152), for an estimated treatment difference of 12.6 %-points (95% confidence interval, 15.3 to 9.8; P<0.0001). More participants in the semaglutide group than in the placebo group achieved weight loss >=5% from baseline at week 104 (77.1% versus 34.4%; P<0.0001). Gastrointestinal adverse events, mostly mild-to-moderate, were reported more often with semaglutide than with placebo (82.2% versus 53.9%). In summary, in adults with overweight (with at least one weight-related comorbidity) or obesity, semaglutide treatment led to substantial, sustained weight loss over 104 weeks versus placebo. NCT03693430"

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Health care economic observation. I have read that some health economists believe that declining rates of cigarette smoking have cost the health care system a lot of money because cigarettes killed a lot of people before they got old enough for really expensive sorts of care.

I ma not sure that obesity is like that because it is not a quick or certain killer.

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Nov 24, 2022·edited Nov 24, 2022

Is the mechanism of action just suppressing hunger? Wondering how this would interact with a bodybuilding-style cut in terms of preserving lean mass, if at all.

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> 10 million Americans on semaglutide (or yet-to-be-approved equally good or superior alternatives) by 2030: 75%

Should this say "at least 10 million..."? (or "at most", or 10±5, or...?)

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I am on Mounjaro, and have been for four months. Lost 20 pounds so far, and I'm not yet on full dosage. Occasional mild nausea but real issue for me is....tiredness. Not fatigue or exhaustion. I'm a former insomniac who can now hit the sack at 9:00 and sleep happily to 6 am, which is insanely weird.

I have been trying to lose weight for 6 years, and for most of that time been in a 20 pound range that is 100 pounds over what someone of my height should weigh. I've eaten 1500 calories a day and not lost a pound, have to drop to 1100 to lose weight verrry slowly (that's with intermittent fasting and low carbs, around 50 grams). Last year before Mounjaro I started intermittent fasting and lost 20 pounds very quickly and then stopped cold. I do not have eating issues. I don't binge. I cut out the "four white foods" six years ago because I learned that I do better on meat and cheese and vegetables than I do on pasta or bread or potatoes and vegetables. I put on weight despite walking two and in some cases four miles a day, which I can do easily.

I am ridiculously healthy and do not have an obesity diagnosis. Stone cold normal readings in A1c, glucose, cholestrol. My doctor sent me to an endocrinologist after I lost 20 pounds and then stopped cold despite the same behavior (which I still do today) because she agreed I might be insulin resistant. Endocrinologist shrugged, said it's multifactorial, but agreed that anyone with my numbers, appearance, and obvious good health was clearly doing everything right and put me on Mounjaro with no further questions. Diagnosis: insulin resistance. My insurance pays around $500 but I'm on the $25 coupon.

I didn't change a single thing about my eating habits and lost ten pounds in 2 months on the low dosage. Higher dosages have finally reduced my appetite somewhat, but my endocrinologist and I have decided to stop the increases at 12.5 (15 is the top) and then maybe even reduce, since my appetite is decreasing but the weight loss rate is constant.

Because I lost weight doing the same behavior and no drop, I'm quite convinced that something far different than appetite suppressing is also going on (fwiw, I was on phentarmine back in the day and liked it fine). Mounjaro is supposed to increase insulin production and reduce the liver's sugar production, although what that means I dunno.

I have no idea what's up with obesity but the idea that it's all about cutting intake and exercise is just stupid. I should have been losing weight for all of the past six years and haven't. Plenty of people eat healthily and are still obese. We're probably the descendants of famine survivors.

Anyway, I wrote about it here: https://educationrealist.wordpress.com/2022/10/09/weight-loss-and-mounjaro

Excerpts:

************

My weight is not considered a health issue. This despite the fact that my weight, for my height, is shocking. Fifty pounds below my highest weight would still leave me medically obese. 50 pounds lost moves me at most one or two clothing sizes. I can lose 30 pounds without anyone noticing.

My height and weight suggests a person needing two airplane seats, XXXXL clothing, wheezing, and inability to climb three stairs. In fact I’m in normal clothing sizes, hike and walk frequently, can run a mile if you make me, and only wheeze because of my allergies. I’m not bragging. My weight bothers me. A lot. But I’m grateful that my appearance suggests I need to lose 30-40 pounds, not 100.

My weight history was quite consistent until 2016. I have a big appetite that didn’t make me fat until I was 30. From that point on, I’d have to cut back my intake every five years or so because the same amount of calories wasn’t burning off reliably. I’d ignore my weight gain until something forced me to acknowledge it, then diet to successfully lose weight I’d keep off for five years or more. My methods are a recitation of conventional food wisdom because I always went to doctors to lose weight.

1992: start exercising, cut way back on fat. That rule, I kept as a guideline until 2016. Kept off for five years.

1997: Fenphen, just in time for the fen to be banned. But phentermine by itself kept working until 2008 or so–that is, slow weight gain but no ballooning. Then my doctor told me I couldn’t have phentermine because of my blood pressure, took me off that and put me on hydrochlorothiazide, which I’ve been on ever since (lisinopril and nifedipine added in 2016). Ending phentermine kicked off a ballooning that I ignored because I was worried that cutting calories wouldn’t work.

2010: I bit the bullet, just cut calories, and lost over 50 pounds in eight months. At that time, I vowed to monitor my weight and not ignore weight problems and over that time did pretty well. I didn’t keep all the weight off, but keeping a scale kept me from ignoring it and I’d cut back and minimize weight gains, even lose a few pounds.

In 2015, I started renting with my brother, which operated on my eating like an invasive species. His leftovers were my undoing: fettucine alfredo, fried chicken, fried fucking porkchops, fresh baguettes, and he keeps peanut butter on hand. That was when I learned that 30+ years of being solely in control of food purchases had created strictures I didn’t even know existed–like don’t buy it and you won’t eat it. It only took me a year to regroup but that year was a 30 pound weight gain and I was back to my all-time high. Wah.

2016 is when the history pattern changed. I cut calories and didn’t lose weight past a given limit. However, two things occurred that year. First, I got much better at watching my weight. I could gain ten pounds from the low limit and then lose them instead of ignoring the problem. Of equal importance, I decided to cut both calories and carbs, which focused me on carbs for the first time since the 70s and the Atkins plan.

*****

The endocrinologist is constantly asking me how my behavior changes, am I eating less, and so on, and is skeptical that I’m dropping weight with no other changes.[note--this was written six weeks ago, before recent dosage increases] My internist is much more friendly to my theory that this drug is changing my body chemistry in some way. Various reddit threads have testimonials to how the drug has stopped the taker’s binge-eating and hunger pangs. None of that applies to me. I wasn’t a binger, had no food issues, and my appetite hasn’t changed much.

My own theory is that changing my carb intake in 2016 took me off the Type 2 diabetes path, but that the insulin resistance path is unaffected by diet changes? Keep in mind I have only a vague idea what insulin does. Science is still the one subject I don’t teach. In any event, if this continues to work, my doctor agrees with me I’ll probably have to take it permanently.

**************************

I'm hoping the cost will come down, but I'm pretty sure my insurance will cover a lot of it, and I'm willing to pay quite a bit to keep weight off. It's all tax-deductible, anyway.

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Losing 10-15% (at best) of one's body weight honestly wouldn't cut it for a large portion of the obese population (15% of 300 lbs puts you at 255, which is still obese). Hearing "you can solve your huge life-altering problem for $15K/year" would be worth it for a lot of people. But hearing "you can solve half of your problem for $15K and then you'll still need a massive amount of effort to finish it off" sounds way less attractive. These drugs may be better than previous solutions but they'd still need to be improved another doubling or more.

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Even given that the pharma company that developed it has a monopoly this pricing seems strange. If it's really on the verge of being prescribed so widely and the company can produce it for a relatively low marginal cost the price charged per dose seems wildly above the profit maximizing price.

More generally, why the hell would they price a drug that's likely to have a large market so high while they don't seem to be extracting the maximum profits from other drugs that have fewer applications but are less likely to be denied by insurance?

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Nov 25, 2022·edited Nov 25, 2022

Should rationalists be more able to lose weight than others? Various people have said something along the lines of, it's obvious that overweight people could lose weight if they stuck with eating less and exercising vigorously. I think that's probably true for most overweight people. Some have health problems that would interfere with their doing vigorous workouts, and a few may have some metabolic quirk that keeps exercise and caloric deficits from taking off the pounds, but I believe that far more than 50% of us could in fact lose weight if we stuck with caloric restriction and increased exercise.

The problem, of course, is that most people fail at sticking to that regimen, including most people posting here today. It seems like most of us must be making simple, obvious errors in our thinking about weight loss regimens when we are on them. Stuff like, today doesn't count -- I deserve a treat -- I'll go back to the regimen tomorrow -- this isn't even going to work, why stick with it?

OK, so it's not motte & baily, but it's simple, obvious errors in reasoning about the situation. Shouldn't rationalists be better than other people at not falling into these thinking errors that lead to abandonment of weight loss regimens?

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Some prescription guidance from Norway. Basically: don't prescribe Wegovy for weight loss yet as we haven't bought the magic injector pens at the right dosage.

I get the need for caution, but does anyone ever make a running tally of the human suffering and mortality caused by bureaucratic foot dragging?

https://relis.no/sporsmal_og_svar/5-6664?source=relisdb

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We see many companies doing this in the Nordics already, there is Embla in Denmark: https://www.joinembla.com/ and Yazen in Sweden: https://yazen.se/

In Denmark this costs ~€200/month and in Sweden it's similar, but this includes virtual doctor's appointments and coaching etc. I believe the actual drug is heavily subsidised by the respective government health systems, but also heavily negotiated with Novo Nordisk, since it's the health system that purchases it centrally for the entire country.

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I’m curious about its effects on alcohol use disorder.

https://www.insider.com/semaglutide-alcohol-addiction-alcoholism-treatment-weight-loss-drug-2022-10

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I have a prescription as a diabetic and I cannot get this since it is always on back order at any pharmacy. I’d love it for weight loss but need it for A1C. How do I solve that?

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If semaglutide reduces ad lib caloric intake by 35% (https://doi.org/10.1111/dom.14280), and 10–40% of the U.S. population wants or would benefit from it, then it seems possible that the "ubiquitous cheap semaglutide" scenario could reduce total food demand in the U.S. by 3–10%. (as a first-order effect—there would probably be second-order effects relating to changes in diet composition, food waste patterns, etc.).

Would this be enough to have appreciable effects on global food prices, agricultural emissions, and farmed animal suffering? Presumably the population that might use semaglutide eats more and has more money than the global average, making their consumption patterns particularly impactful. Perhaps EAs focused on farmed animal suffering should be trying to nudge the trajectory towards ubiquitous cheap semaglutide; it's not every day one finds an opportunity to reduce demand for meat by 5% without asking consumers to make any sacrifices!

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I use Saxenda for a year now, list price is 500 Canadian dollar per month but with Manulife insurance im payong 100/ per month.

I lost 25 kg in the first 6 months, then I felt "acclimated" to the drug and started eating a lot again. Seeing that the drug is no longer working I stopped. You feel nausea using this drug at first, when the nausea subside the drug is not working anymore for me.

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I'm not at all opposed to people using this if it helps and the side-effects aren't too bad. I'm on Adderall, so I'm certainly not one to talk. But even if it does... They still need to exercise. It's the most important thing you can do if you want to be happy, improve your mood, optimize your cognitive and physical functioning... There's so much focus on weight loss, which is understandable given the epidemic of obesity, but to lose weight isn't even anywhere near the top of the list of reasons to exercise. Intermittent fasting is easier and more effective for just weight loss IMO anyway.

"In a 2017 essay, Norwegian ethicist Sigmund Loland posed the question: If it becomes possible, should we replace exercise with a pill? Scientists are already trying to manufacture medicines that mimic the health benefits of exercise. What if they succeed? “Considering exercise takes time and energy and usually financial resources in addition to implying a risk for injury, the only reason for not replacing exercise with a pill must be related to values in the very activity of exercising in itself,” Loland writes. “Does exercise have such values, and if so, what are they?”

"Based on what I’ve learned from the science and stories that fill this book and from my own direct experience, I would say the answer is a resounding yes. Movement offers us pleasure, identity, belonging, and hope. It puts us in places that are good for us, whether that’s outdoors in nature, in an environment that challenges us, or with a supportive community. It allows us to redefine ourselves and reimagine what is possible. It makes social connection easier and self-transcendence possible. Each of these benefits can be realized through other means. There are multiple paths to self-discovery and many ways to build community. Happiness can be found in any number of roles and pastimes; solace can be taken in poetry, prayer, or art. Exercise need not replace any of these other sources of meaning and joy. Yet physical activity stands out in its ability to fulfill so many human needs, and that makes it worth considering as a fundamentally valuable endeavor. It is as if what is good in us is most easily activated by or accessed through movement. As rower Kimberly Sogge put it, when she described to me why the Head of the Charles Regatta was such a peak experience, “The highest spirit of humanity gets to come out.” Ethicist Sigmund Loland came to a similar conclusion, declaring that an exercise pill would be a poor substitute for physical activity. As he wrote, “Rejecting exercise means rejecting significant experiences of being human.”"

McGonigal, Kelly. The Joy of Movement (pp. 212-213). Penguin Publishing Group. Kindle Edition.

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I am a psychiatry resident and am interested in semaglutide as a method of counteracting the metabolic side-effects of second-generation antipsychotics (SGAs), and most prominently the so-called "-pine" drugs: olanzapine, quetiapine, and clozapine. These drugs are fairly effective antipsychotics, but many are hesitant to take them and/or stop taking them due to weight gain. I spoke to an endocrinologist from Columbia University Hospital who said that the psychiatry department there occasionally consults endocrinology to start patient's on semaglutide at the same time as starting an SGA if the patient is already obese. None of my attendings are willing to do this and I have never heard of any other psychiatrists doing it, but I think it is an interesting idea. Scott, have you considered doing this in your practice? Have you seen others doing it? If not, why? A drug that can counteract the metabolic side-effects of SGAs could potentially change psychiatry and would be one of the biggest boosts to compliance in the history of the field.

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It was my understanding that Yagmuk just can't read english specifically, not that he is fully illiterate. Have I had the lore of this selfless hero wrong this whole time?

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My understanding was that this works by causing such intense nausea that patients have difficulty eating enough to stay fat.

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I am an internist with a longstanding interest in the medical management of obesity. 

Bariatric surgery keeps getting better and better and safer and safer. A Sleeve Gastrectomy in the year 2022 is safer that a gall bladder extraction, a hysterectomy or even a TURP for benign prostate disease.

We now have strong evidence from several high quality prospective studies that obese patients who have bariatric surgery live longer and have much higher quality of lives than carefully matched patients who don’t. If I experienced biliary colic, I would not hesitate to have my gallbladder removed. If I was a woman and I had severe menorrhagia or painful periods, I would not hesitate to have a hysterectomy. 

IFSO and the ASMBS, the two largest bariatric surgical associations in the world, recently updated their guideline recommendations for the first time in 30 years. They are now recommending that all patients with a BMI of 35 (except for the occasional weight lifter) should consider bariatric surgery as well as all diabetics with a BMI of 30 (about 90% of diabetics) and that surgery can even be considered in selected patients with no co-morbidities.

I completely support those recommendations. I recently posted a 17 minute highly evidence based discussion on bariatric surgery on YouTube which I think might interest you.

Ronald Eliosoff MD, FRCP

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I am a huge fan of semaglutide and here in Canada, it is really not that expensive (about $3,000 /year).

However, for a one-shot payment of $14,000, one could get a Sleeve Gastrectomy by a world class bariatric surgeon. After that the need for meds for diabetes hypertension, arthritis, depression and heart disease all plumet!

From a societal perspective, the cost savings would be incalculable.

I have posted on YouTube a video of a presentation that I gave at an international bariatric surgery conference in which I argued that bariatric surgery pays for itself in less than one year!

Ron Eliosoff MD, FRCP

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One-off GLP-1-proximal treatments may be sufficient for significant mitigation of obesity. If this bears out, would significantly alter the cost-benefit calculus. https://twitter.com/DanielJDrucker/status/1591171488002232320?s=20&t=HWuGywdinWSLxCtYDJva2A

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One interesting tidbit about Mounjaro's discount program:

Through November, Mounjaro's manufacturer coupon was really generous. You'd bill the primary insurance first and, after getting a rejected claim)/request for a prior authorization, bypass the initial payer and receive a pay amount of $24.99. You didn't need an actual insurance authorization, just proof of insurance to be eligible.

However, it appears this deal is ending. The most recent claim I processed (Monday or Tuesday evening) came back with a patient pay amount over $500 after bypassing the initial payer. Upon calling the pharmacy help desk, the representative informed me that patients with new coupons (anything after mid-november) would have to pay the elevated price sans insurance approval, and that the preexisting $24.99 coupons would be grandfathered in.

Thus, it looks like new patients seeking Mounjaro will need a PA before seeing an affordable price. It's too bad from a pharmacy standpoint, given how much easier it was to bill the drug without getting insurance providers involved.

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I predicted back in April that the plethora of obesity-drugs found with A.I. assistance in the next FIVE years would be sufficient to cause a wave of angst against the Pharmafia, such that cheap knock-offs or price-competition finally come into play. We'll see if who's right!

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> “Where are the compounding pharmacies getting it?”

There are peptide synthesis companies a compounding pharmacy could contract with. The sequence is known. I figure this is what they’re doing, since…

> ways to get it cheaper

Some of these peptide companies are selling (cheaper but still expensive) semaglutide to consumers for “research purposes only”.

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In this context, the transhumanist argument is not very convincing. The technology to lose weight already exists. It's called "healthy food". It's widely available and not patented.

The magical weight-loss pill is meant for people who do not want to use healthy food as a weight loss method. Instead of eating healthy, they want to consume psychoactive drugs which contain also lots of calories. Those are called "junk food".

The primary problem is dealing with the addiction to junk food. That's a serious mental health problem.

Maybe the transhumanist solution would be the development of new psychoactive drugs that won't cause enormous health problems to the users. People could add them to healthy food in order to consume it instead of junk food.

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Just as a point of information, my Medicare Advantage plan covers Ozempic with a 20% copay which was $94 for the first prescription and $47 thereafter at CVS so I think the $1,000 price is not correct. I think uptake will be very fast among those of us over 65.

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I don't think you'd need more than 10% or whatever of people to take the drug to have a large effect on obesity in general.

Very smart people in the comments have noticed that obesity is caused by eating too much food, and that the permanent cure to it is to eat less food. This has the great advantage of being true, but is incredibly unhelpful to the people who actually are obsese. That's really hard, and it's hard for a lot of psychological reasons and social reasons and structural reasons that have a lot less to do with personal willpower and a lot more to do with what everyone else is doing around you. You don't eat because you're hungry, you eat because it's there/you're tired/everyone else is doing it/you're used to it. Exercising and increasing activity suffers from the same problem: it's not that you don't want to exercise, it's that it's hard and nobody else is doing it so there's no immediate profit to doing so.

However, if the hype is real and semaglutide really works like that, it sounds like it removes a lot of the social/psychological pressures and lets your body's metabolism figure out how much you need to eat without all the extra noise. It's a lifestyle drug, not a weight-loss drug. If you had a drug that, say, can make people walk around the block every day after dinner, you'd get a similar result. (At least, in my limited understanding of the actual mechanics here).

Obese people tend to travel in the same circles as other obese people for obvious social and economic reasons. If you could take 10% of those people and cause them to magically change their lifestyles (say, by giving them a drug or something), you'd have spillover effects within their social circles. This isn't just that the family goes to a salad bar instead of the fried cheese palace for dinner (although that will probably help on the margins), it's dumb but important stuff like how they see themselves and what they think is possible and even guilt about losing weight because you'll be making yourself "better than" your friends/family. (I've heard this from several obese and formerly obese people, including my mother, this sentiment is *shockingly* common). If your friend or family member is losing weight and you can see them feeling better and they're less likely to indulge in behaviors like overeating when they're around you, you have a model for instigating those same lifestyle changes and the motivation to do so.

You don't need everyone to take the drug, you just need a small population to change their lifestyles enough that their social circles can follow suit. Does the snowball effect eliminate obesity in burgerstan? Probably not, but it could be a serious factor and reduce obesity rates much more than the 10% of semaglutide users would indicate.

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How does this compare to the bodybuilding drug Clenbuterol aka Clen? "Eat Clen tren hard" is a meme for a reason.

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For what it's worth, I use a similar savings card for a far more expensive medication, and it basically does what it says on the tin, no weird gotchas. In fact, mine's better, it brings the out-of-pocket cost down to $5 and has no limit on monthly rebates.

It's basically a dance where the medication company says "we'll sell you this drug for *a million bajillion dollars* and not a cent less! but your patient needs it, so you must pay!" and the insurance company says "well, we'll cover $4,000 dollars, the patient can pay the rest" and the medication company says "the *patient*? have you no *pride* in the health of our citizens? why, out of the goodness of our hearts, *we* will altruistically cover the rest! also thanks for the four grand".

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Compounding pharmacist here:

1) I’m not certain where other folks are getting semaglutide, but I would imagine Chinese pharma companies. You may have heard of the pharmacy in SLC, UT that attempted to compound hcq for COVID and sell it to the state of Utah? He bought it from a Chinese pharma company and what he eventually got busted for was false shipping manifests, not the blatant violation of the FDCA. I imagine something similar happened here.

2) while I can’t speak to the legality of sourcing the active ingredient, preparing the compound is probably legally fine. Wegovy and Ozempic has been in a shortage state for nearly 2 years now. In cases of shortages, I CAN legally compound products, including those protected by a patent or otherwise theoretically available. Patient access comes first- if I can’t source a finished product due to the manufacturer not having adequate supply, I’m good. I have to maintain documentation of my inability to source the patented products or the otherwise available product, but this is accepted practice. See, for example, this week’s FDA GFI re: compounding amoxicillin suspension for kids.

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Really enjoyed this article, didn’t know much about these drugs post-Elon mentioning he uses them.

As someone who eats healthy, works out a lot and still struggles to lose weight, seems like a really great option for millions of people in the same camp trying to live their best lives.

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I'm on it (have been for the past 1.5 mo) and have taken two prior "cycles" going a few years back. The effects described on the Reddit screenshots are pretty much what I've felt. On the side-effect side, on a previous attempt at starting the current cycle (maybe 3mo ago) I've had such an upset stomach that it felt just like it feels when I'm extremely anxious (say, before giving a talk or starting an Ironman)... in a very bad way, so bad that the feeling reminded be of my worst days of depression. Anyway, I started on a higher dose (.5mg) straight away; on this current attempt, I started at .1mg, and increased dosage *very* slowly, so that I'm only now reaching .5mg.

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When I was working at an outpatient hospital pharmacy briefly in Bakersfield we had tons of medical residents writing Ozempic prescriptions for themselves so they could get it for cash cheap with a huge 340B discount (I want to say it was something ridiculous like $400ish per month). We had to constantly reprimand them not because they were outrageously abusing 340B but because almost all of them were doing it incorrectly by not having their attending document an office visit and then writing the prescription for them.

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The pancreatitis thing worries me with semaglutide. There's already a huge spike in that going on that is poorly understood, and as someone who got hit with it last year, it appears to have permanently effed my digestion, even as mild an episode as it was (no walled necrosis or multisystem organ failure). Ironically, I did lose a ton of weight (who knew permanent exocrine damage was so good for the waist line?). Anyways, I'm probably overly sensitive to that risk, given personal trauma, but at the same time, given the already rising tide of pancreatic issues, it would seem that putting 10s of millions of people on this drug might be a tough situation. But maybe the risk is small enough its ok. I've not seen any hard number put to it anywhere so I don't really know how to judge it.

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Nov 29, 2022·edited Nov 29, 2022

In Portugal the price of the drugs is available publicly on Infarmed's website (the Portuguese counterpart for the DA part of the FDA).

Wegovy is not yet being sold here, but the price for Ozempic is 120€/month. The government supports 90% of that, and the patient the other 10%. I believe that for Wegovy, the patients will have to pay the whole amount (or have some health insurance pay it, but I think that's unlikely).

https://extranet.infarmed.pt/INFOMED-fo/detalhes-medicamento.xhtml?med_guid=255e52d08c2411e8897bb0491981aaed

Edit: I've seen a chinese pharma that seems legit enough selling it for 50$/month (considering the weekly dosage of 2.4mg, while Novo Nordisk is selling in Portugal for 120€/month the 1mg dosage)

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Ozempic 1g /week one year. 5'10". From 285 lb to 265lb.

Stopped because of hepatic pains getting consistently relatable post injections.

Worked by aversion mechanism to fat , permanent bloated uncomfortable feel, and making sugary things very unappealing ( which are to me anyway).

After being miserable and ( more ) depressed , I stopped it.

Next week I finally enjoyed my favourite cheeses and sourdough.

Never ever eating fast food, greasy spoon , buffet. Gourmandly hedonistic ( lived all over the world ( Europe mostly) and that's actually a curse.

I gained 16 back ( within two month). Now I'm shedding 2 lb/ month just doing portion control ( inflation and scarcity ) helps . At this pace , in 3 yrs will be overweight ( BMI 29.5) . In 6 yrs within normal ( BMI 24). Then retirement and ensuing poverty will potentially be contributing factors to go at the 20-21 BMI . If I won't die until then, that's my plan.

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Why take drugs to lose weight?

(Taking drugs means to eat more - whereas losing weight means to eat less.)

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There's gut bacteria that result in increased GLP-1 production in response to food intake.

I suspect some people just have a lot of these. Something happened in environmental factors to kill a lot of these in people. Semaglutide works by replacing the lost endogenous GLP-1.

https://www.nature.com/articles/s41598-020-61112-0

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Rybelsus is much cheaper here in Brazil. A box of 30 pills 3mg (with manufacturer coupon) cost like U$ 50. 7 mg would be around U$ 110 and 14mg about U$ 200.

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RE: What About Europe And The Rest Of The World?

In Denmark, the home country of Novo Nordisk, Wegovy litterally just arrived on the market the other day. The price is around DKK 1,500 (~$200) per month.

The Danish health authorities have denied the application for public subsidies for the drug, citing that the price is too high, lack of evidence of the long-term effects, and lack of evidence of effectiveness against cardiovascular disease.

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lol i've been on it for over 14 months and it costs me a little over $40 per week (NO INSURANCE). This article is ridiculous

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Are the percentages following the predictions in postscript four some sort of confidence estimate?

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