Astral Codex Ten

tirzepatide

40 min read

tirzepatide

Article

tirzepatide is a recurring brand in the Astral Codex Ten archive, appearing 5 times across 5 issues between December 20, 2021 and March 12, 2025. The archive places it in contexts such as “promise of two new research chemicals, tirzepatide and bimagrumab”; “Eli Lilly owns a closely related molecule, tirzepatide (Mounjaro®)”; “Lilly’s tirzepatide”. It most often appears alongside FDA, semaglutide, Eli Lilly.

Metadata

  • Category: Brands
  • Mention count: 5
  • Issue count: 5
  • First seen: December 20, 2021
  • Last seen: March 12, 2025

Appears In

Source Context

Recovered passages from the original issue text. When the raw archive preserved outbound links inside the source passage, they are listed directly under the quote.

Mantic Monday: Let Me Google That For You
December 20, 2021 · Original source
So for example, when Stephan talks about the promise of two new research chemicals, tirzepatide and bimagrumab, he’s able to punctuate his points with these graphs:
Semaglutidonomics
November 24, 2022 · Original source
The first analysis asks “what if doctors medicalized obesity as comprehensively as they’ve medicalized hypertension and high cholesterol?” That is: what if we put in a society-wide effort to get every obese person to a doctor, and after only a little diet and exercise, the doctor puts them on a medication? They find that the US obesity market would multiply by a factor of 25, to about $87 billion/year. The second analysis is a more realistic projection for the next decade. Two things stand out. First, the number of patients on Wegovy or related medications goes from an estimated 46,910 now (pretty close to my 50,000 estimate!) to 11.3 million in 2030. Second, the cost per prescription goes from $15,000/year to about $4,000 year. Let’s look at this second change in more detail. Right now semaglutide is literally in a class of its own for weight loss. But remember, it started as a GLP-1 agonist diabetes drug. And there are other GLP-1 agonists already in use for diabetes. Novo Nordisk’s competitor Eli Lilly owns a closely related molecule, tirzepatide (Mounjaro®). They’ve already done studies showing it also works very well for weight loss - if anything even better than semaglutide - and they’re expected to get FDA approval to market it as a weight loss medication next year. Although capitalism fans might expect the presence of two competing drugs to immediately drive down prices, this is mysteriously not how things work in health care and prices will probably stay the same in the short term. But several other companies are working on semaglutide-like drugs, some will be cheaper to produce than semaglutide, and Morgan Stanley expects that this stronger level of competition will eventually drive costs down to $350/month ($4,000/year) by 2030. “Mounjaro” sounds like the playful animal sidekick in a Disney movie. From a purely economic perspective, semaglutide costs the health system money (because it’s expensive) but also saves the health system money (because we don’t have to pay for obesity consequences like diabetes and heart attacks). Which effect wins out? According to the Institute for Clinical and Economic Review, benefits would outweigh costs if semaglutide cost less than about $8,000/year. Since it costs $15,000 year now, it’s not cost effective. But if Morgan Stanley’s model comes true and it costs $4,000/year in 2030, then it will be cost effective. So at some point, Medicare (and so insurance companies) may start covering it more out of self-interest. I can’t tell whether the model takes this into account or not. (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.) 11.3 million prescriptions at $4,000/year comes to $45 billion, but Morgan Stanley expects that not everyone will fill their prescriptions consistently or stay on the medication the same amount of time, leading to their $31 billion figure. Towards The Glorious Post-Obesity Transhuman Future The Morgan Stanley report shows that even the greediest pharma investors, openly plotting to medicalize obesity, can’t bring themselves to believe in more than 11 million US semaglutide patients by 2030. That’s less than 10% of the US obese population. Isn’t that kind of disappointing? We’ve got > 100 million people dealing with a condition that not only makes them unhealthy, but also causes them psychological distress, and makes lots of people low-grade disappointed in and repulsed by our society. And we’ve got an effective drug that treats the condition. And we’re going to use it on less than 10% of the people involved? In 2032, semaglutide goes off-patent. It will probably take a few years to sort out legal issues and ramp up generic production, but by the mid-2030s, its price will go way down. I don’t think there are technical barriers to getting it down as low as $10 - $100 per month. By then, maybe there will be even more exciting branded weight loss drugs for wealthy people to choose from. But at the very least, semaglutide itself should become much more widely available even to poor or uninsured patients. I’m not sure what will happen. Will there be an inflection point, where so many people use semaglutide that obesity becomes unusual again, and then the remaining obese people start using it just to fit in? Will obesity become an optional fashion statement, like shaving your head or getting a tattoo? Or will semaglutide end up disappointing us in some way, like so many promising drugs have before? 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 this will happen, but for the first time I can see a clear path to how it might. Postscript 1: Should You Take Semaglutide? I can’t answer this, please ask your doctor. But I do want to add that there are potential side effects I haven’t mentioned in this post, including nausea, gastrointestinal problems, pancreatitis, and kidney problems. Semaglutide has been accused of slightly increasing risk of pancreatic and thyroid cancers. Studies have found trends in this direction, but these conditions are so rare that even over thousands of patients over many years, the increase hasn’t yet reached clear statistical significance. The current consensus position is that it may increase thyroid cancer by a tiny amount not relevant to most patients, and that it probably doesn’t increase pancreatic cancer. I think my father has looked over these data more and is less sure than other people about the lack of pancreatic cancer risk, but he can’t get the resources he needs to prove anything, and I can’t remember his exact argument. More broadly: like all medications, semaglutide has benefits and risks, and you shouldn’t blindly take it after reading one blog article. Postscript 2: Is There A Way To Cheat The System To Get Semaglutide For Lower Cost? Health care is much like airline tickets: everyone pays a different price for everything and there’s usually a secret way to get what you want for much less money. Is this true of semaglutide? Pharma company Novo Nordisk offers a Savings Card that they say brings the price down to as low as $25 per month. I’m a little suspicious of this - pharma company offers are rarely as good as they sound - but I don’t notice any obvious tricks in this one and it should probably be your first bet. This startup claims that they can get insured people semaglutide for a $25/month copay “after their deductible is met” by negotiating with the insurance company very effectively. I can’t imagine how that works or what they have to negotiate with, but they seem pretty convinced, so I would welcome more information. Otherwise, you don’t have many great options. Although there are two older forms of semaglutide not FDA-approved for weight loss - Ozempic and Rybelsus - these are both more expensive, milligram per milligram, than Wegovy itself. Canada is also of no help. The usual Canadian pharmacies don’t seem to carry Wegovy, and charge about the same amount for Ozempic as American pharmacies do. This article in Drug Discovery Trends says that compounding pharmacies have been selling semaglutide for $300/month, less than a quarter of the sticker price. This is a bit confusing: compounding pharmacies are small local operations permitted to dispense unusual medications by mixing existing ones together in nonstandard ways. They’re arguing that they can legally dispense the semaglutide because they’re mixing it with vitamins, which, fine, but how are they getting it in the first place? Everyone else seems as confused as I am: "Nobody knows how [compounding pharmacies are] getting it," said Karl Nadolsky, an endocrinologist at Spectrum Health. "Who's making it? [The pharma company that makes it] Novo [Nordisk]'s not giving it to them. They're the ones with the rights to the molecule, so how is anybody getting semaglutide?" Has nobody asked compounding pharmacists about this? Do they have a conspiracy of silence? Does the FDA sometimes send their goons in to extract the information, but the compounding pharmacists compound sleeping gas / smoke grenades and vanish into the night? Anyway, the usual authorities warn you not to take compounded semaglutide under any circumstances, but they’re the same people who tell you never to buy drugs from a Canadian pharmacy because they might be adulterated. You can decide how much you want to trust them. Postscript 3: What About Europe And The Rest Of The World? Countries that are not the US usually negotiate with pharmaceutical companies over price. Because of some combination of “negotiation works” and “they are free-riding off Americans’ hard work”, they usually get much lower prices. What does semaglutide cost elsewhere? This is hard to find out because government health agencies sometimes keep their prices secret, plus Wegovy mostly isn’t available in other countries yet. The only information I could find was from Britain, which is in the process of making Wegovy available to patients. It looks like NHS will “restrict the expensive drug’s availability to very obese people attending specialist weight-loss clinics”, but that it might be possible to get it from private clinics for £199/month = £2400/year. Wegovy has been approved in the EU but doesn’t seem to have made it there yet. I can’t find any information about any other country. Non-weight-loss-indicated versions of semaglutide are available in many countries, but I wouldn’t expect their health care systems to be flexible about redirecting it for weight. Canadian regulators have approved Wegovy, but it doesn’t seem to be available there yet. I haven’t seen any evidence that Ozempic costs less in Canada than it does in the US, and I’m not sure why. Maybe the pharma companies have figured out that anything that happens in Canada gets imported into the US, and they’re playing hardball this time. I don’t know whether Canadians will be able to get it for cheaper than Americans or not. Postscript 4: Predictions (all predictions are conditional on no singularity or global catastrophe) 10 million Americans on semaglutide (or yet-to-be-approved equally good or superior alternatives) by 2030: 75%
Inline links: this is mysteriously not how things work in health care, https://substackcdn.com/image/fetch/$s_!5poy!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fbucketeer-e05bbc84-baa3-437e-9518-adb32be77984.s3.amazonaws.com%2Fpublic%2Fimages%2Fc201f05a-7d1f-4738-911f-11d0d051adf9_2880x1562.png, Institute for Clinical and Economic Review, don’t think there are technical barriers, offers a Savings Card, This startup, about the same amount for Ozempic, This article in Drug Discovery Trends, Everyone else seems as confused as I am, NHS will, private clinics
“Mounjaro” sounds like the playful animal sidekick in a Disney movie. From a purely economic perspective, semaglutide costs the health system money (because it’s expensive) but also saves the health system money (because we don’t have to pay for obesity consequences like diabetes and heart attacks). Which effect wins out? According to the Institute for Clinical and Economic Review, benefits would outweigh costs if semaglutide cost less than about $8,000/year. Since it costs $15,000 year now, it’s not cost effective. But if Morgan Stanley’s model comes true and it costs $4,000/year in 2030, then it will be cost effective. So at some point, Medicare (and so insurance companies) may start covering it more out of self-interest. I can’t tell whether the model takes this into account or not. (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.) 11.3 million prescriptions at $4,000/year comes to $45 billion, but Morgan Stanley expects that not everyone will fill their prescriptions consistently or stay on the medication the same amount of time, leading to their $31 billion figure. Towards The Glorious Post-Obesity Transhuman Future The Morgan Stanley report shows that even the greediest pharma investors, openly plotting to medicalize obesity, can’t bring themselves to believe in more than 11 million US semaglutide patients by 2030. That’s less than 10% of the US obese population. Isn’t that kind of disappointing? We’ve got > 100 million people dealing with a condition that not only makes them unhealthy, but also causes them psychological distress, and makes lots of people low-grade disappointed in and repulsed by our society. And we’ve got an effective drug that treats the condition. And we’re going to use it on less than 10% of the people involved? In 2032, semaglutide goes off-patent. It will probably take a few years to sort out legal issues and ramp up generic production, but by the mid-2030s, its price will go way down. I don’t think there are technical barriers to getting it down as low as $10 - $100 per month. By then, maybe there will be even more exciting branded weight loss drugs for wealthy people to choose from. But at the very least, semaglutide itself should become much more widely available even to poor or uninsured patients. I’m not sure what will happen. Will there be an inflection point, where so many people use semaglutide that obesity becomes unusual again, and then the remaining obese people start using it just to fit in? Will obesity become an optional fashion statement, like shaving your head or getting a tattoo? Or will semaglutide end up disappointing us in some way, like so many promising drugs have before? 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 this will happen, but for the first time I can see a clear path to how it might. Postscript 1: Should You Take Semaglutide? I can’t answer this, please ask your doctor. But I do want to add that there are potential side effects I haven’t mentioned in this post, including nausea, gastrointestinal problems, pancreatitis, and kidney problems. Semaglutide has been accused of slightly increasing risk of pancreatic and thyroid cancers. Studies have found trends in this direction, but these conditions are so rare that even over thousands of patients over many years, the increase hasn’t yet reached clear statistical significance. The current consensus position is that it may increase thyroid cancer by a tiny amount not relevant to most patients, and that it probably doesn’t increase pancreatic cancer. I think my father has looked over these data more and is less sure than other people about the lack of pancreatic cancer risk, but he can’t get the resources he needs to prove anything, and I can’t remember his exact argument. More broadly: like all medications, semaglutide has benefits and risks, and you shouldn’t blindly take it after reading one blog article. Postscript 2: Is There A Way To Cheat The System To Get Semaglutide For Lower Cost? Health care is much like airline tickets: everyone pays a different price for everything and there’s usually a secret way to get what you want for much less money. Is this true of semaglutide? Pharma company Novo Nordisk offers a Savings Card that they say brings the price down to as low as $25 per month. I’m a little suspicious of this - pharma company offers are rarely as good as they sound - but I don’t notice any obvious tricks in this one and it should probably be your first bet. This startup claims that they can get insured people semaglutide for a $25/month copay “after their deductible is met” by negotiating with the insurance company very effectively. I can’t imagine how that works or what they have to negotiate with, but they seem pretty convinced, so I would welcome more information. Otherwise, you don’t have many great options. Although there are two older forms of semaglutide not FDA-approved for weight loss - Ozempic and Rybelsus - these are both more expensive, milligram per milligram, than Wegovy itself. Canada is also of no help. The usual Canadian pharmacies don’t seem to carry Wegovy, and charge about the same amount for Ozempic as American pharmacies do. This article in Drug Discovery Trends says that compounding pharmacies have been selling semaglutide for $300/month, less than a quarter of the sticker price. This is a bit confusing: compounding pharmacies are small local operations permitted to dispense unusual medications by mixing existing ones together in nonstandard ways. They’re arguing that they can legally dispense the semaglutide because they’re mixing it with vitamins, which, fine, but how are they getting it in the first place? Everyone else seems as confused as I am: "Nobody knows how [compounding pharmacies are] getting it," said Karl Nadolsky, an endocrinologist at Spectrum Health. "Who's making it? [The pharma company that makes it] Novo [Nordisk]'s not giving it to them. They're the ones with the rights to the molecule, so how is anybody getting semaglutide?" Has nobody asked compounding pharmacists about this? Do they have a conspiracy of silence? Does the FDA sometimes send their goons in to extract the information, but the compounding pharmacists compound sleeping gas / smoke grenades and vanish into the night? Anyway, the usual authorities warn you not to take compounded semaglutide under any circumstances, but they’re the same people who tell you never to buy drugs from a Canadian pharmacy because they might be adulterated. You can decide how much you want to trust them. Postscript 3: What About Europe And The Rest Of The World? Countries that are not the US usually negotiate with pharmaceutical companies over price. Because of some combination of “negotiation works” and “they are free-riding off Americans’ hard work”, they usually get much lower prices. What does semaglutide cost elsewhere? This is hard to find out because government health agencies sometimes keep their prices secret, plus Wegovy mostly isn’t available in other countries yet. The only information I could find was from Britain, which is in the process of making Wegovy available to patients. It looks like NHS will “restrict the expensive drug’s availability to very obese people attending specialist weight-loss clinics”, but that it might be possible to get it from private clinics for £199/month = £2400/year. Wegovy has been approved in the EU but doesn’t seem to have made it there yet. I can’t find any information about any other country. Non-weight-loss-indicated versions of semaglutide are available in many countries, but I wouldn’t expect their health care systems to be flexible about redirecting it for weight. Canadian regulators have approved Wegovy, but it doesn’t seem to be available there yet. I haven’t seen any evidence that Ozempic costs less in Canada than it does in the US, and I’m not sure why. Maybe the pharma companies have figured out that anything that happens in Canada gets imported into the US, and they’re playing hardball this time. I don’t know whether Canadians will be able to get it for cheaper than Americans or not. Postscript 4: Predictions (all predictions are conditional on no singularity or global catastrophe) 10 million Americans on semaglutide (or yet-to-be-approved equally good or superior alternatives) by 2030: 75%
Inline links: Institute for Clinical and Economic Review, don’t think there are technical barriers, offers a Savings Card, This startup, about the same amount for Ozempic, This article in Drug Discovery Trends, Everyone else seems as confused as I am, NHS will, private clinics
Highlights From The Comments On Semaglutide
November 30, 2022 · Original source
I think those numbers might be "over one year", and they could stay on it longer than a year. I was kind of lazy just asserting “drugs might get better”, but I think the upcoming CagriSema combination and AMG-133 are good examples of how this might play out. Max Görlitz has done the proper thing and made Manifold markets for each of my predictions - see here, here, here, here, and here. Despite the problems with prediction markets for decades in the future, the “will obesity be cut in half by 2050” one seems popular: 5. Do You Have To Stay On Semaglutide Forever Or Else Gain The Weight Back? Biff_Ditt writes: I saw on the 1 year follow-up to the STEP-1 trial that most of the participants gained all of their lost weight back. Biff is probably thinking of Weight Regain And Cardiometabolic Effects After Withdrawal Of Semaglutide, which finds people gained back 2/3 of the lost weight after a year. The graph looks like it’s in the process of plateauing but not quite there, so I don’t know if we should expect them to regain the other third later. This matches what I would expect from my understanding of other diets and weight loss drugs. Still, some people disagree. Maximum Liberty writes: Anecdote is not the singular of data, but my better half lost 25 pounds on it, then had to get off it for reasons unrelated to the drug. She has not regained the weight yet -- and consistently eats less now that she had for years. So in at least one case, the drug helped with a successful change in eating habits. Lauren Thomas writes: So there's been a lot of research on dieting and losing weight, etc., and one of the things that has been found is that your body has a "set" point weight wise that it will try REALLY hard to return you to. If you lose weight, your body will slow its metabolism until you return to that weight. If you gain weight, your body will rev up metabolism. That's why you might gain 10 lbs over Christmas and then lose it in January without purposefully trying to lose weight. (this is all in the short term, ofc, as people do tend to naturally gain weight as they age). This seems to imply that semaglutide would need to be taken forever. However, there seems to be an important caveat: you *can* reset your set point, it just takes a long time at the new weight. When most people go on diets and lose weight, they end up regaining the new weight quite quickly after they "end" their diet, so they don't have a chance to reset their set point. Speaking from personal experience, I had kind of an accidental natural experiment with this: I once lost 40 lbs over the course of a year and a half, where I began with a very strict low carb diet that very very slowly trailed off to a normal diet, mostly because I got progressively more tired of being on the low carb diet. So by the time I had gotten back to my normal diet, I had been losing weight for a long time. I ended up regaining 10 lbs of the weight, but no more, and am still ~30 lbs below my peak even today (5 years later). Something like this has been my experience with dieting too so far. And something like set point reset has to exist in order to explain things like why so many obese people fail to lose weight after they start eating healthy, and maybe other things like anorexia. And maybe it works for some people. Still, the evidence suggests that most people who stop semaglutide will regain the weight, at least for the protocol used in the study. Maybe some other protocol that had them on it for more than a year would have done better? 6. Personal Anecdotes Edgehopper writes: 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. Education Realist (blog) writes: 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 Eliezer Yudkowsky writes: 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. Lan writes: 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.) Walter Sobchak, Esq writes: 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. 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. Also from Walter, and I was wondering about this: I was very concerned with the injections before I started Wegovy. My experience is that the injector is fast and almost painless. My pharmacist was important because he showed me how to do it correctly before I started. 7. Tangents That I Find Tedious, But Other People Apparently Really Want To Debate Why can’t people just diet and exercise? (142 comments)
Inline links: here, here, here, here, here, writes, Weight Regain And Cardiometabolic Effects After Withdrawal Of Semaglutide, writes, writes, anorexia, writes, Education Realist, blog, https://educationrealist.wordpress.com/2022/10/09/weight-loss-and-mounjaro, writes, writes, from Walter, Why can’t people just diet and exercise?
Links For January 2025
January 17, 2025 · Original source
I agree with this solution. 3: Ruxandra Teslo and Willy Chertman: The Case For Clinical Trial Abundance 4: This month in nominative determinism: NYT article calculating your chance of winning the lottery, by Victor Mather (h/t Yafah Edelman). 5: Someone is working on a dating site that uses your conversations with Claude to find a match. Link here, although so far it’s just a landing page where you can register interest (h/t @venturetwins) 6: The Lyttle Lytton Contest searches for the worst possible opening line for a novel; it’s been going on since 2001 and this year’s results are in. 7: Gary Marcus and Miles Brundage have made a bet about AI progress. I agree with @tamaybes and others in saying that Miles let Gary off too easily; Gary’s public statements all sound like “modern AI is mostly hype, it doesn’t really do anything like thinking”, but the bet is about things like “will AI make a Nobel Prize caliber scientific discovery by 2027?” and “will AI write Pulitzer-quality books by 2027?” I don’t blame Gary for taking the best terms he could find. But I am worried that if AI makes a Nobel-quality scientific discovery in 2026, but doesn’t quite write the Pulitzer-quality book, then Gary will get to claim victory over the AI optimists, whereas in fact that would be at probably the 95th percentile of fast timelines by most people’s estimate. 8: “The probability that cows (or other non-human animals) are experiencing constant bliss, lack tanha (craving, aversion, and the resulting suffering), or are "enlightened by default" is, by my estimation, very low”. 9: Recursive Adaptation (blog on addiction policy)’s predictions for 2025. 75% of FDA approval of GLP-1 for a substance use disorder by 2029! 10: In my post on the economics of GLP-1 receptor agonists (eg Ozempic), I wrote about how they’re currently widely available because of a loophole suspending patents during a shortage, and predicted there would be a big fight when the shortage was over. Sure enough, the FDA tried to declare that the shortage of tirzepatide (a next-generation Ozempic relative) was over, compounding pharmacies sued, and tirzepatide is still available while the issue goes through the courts (and will the administration have an opinion?) Also, compounding pharmacy access startup Mochi says that they will continue to prescribe even if the shortage is over, using another loophole saying doctors can do this for specific individual patients in cases of medical necessity. This is an extremely fake use of this loophole, but will the government be willing to call their bluff? 11: Jacob Falkovich has a blog on dating advice, which he plans to turn into a book of dating advice. I can’t really comment on the accuracy (my dating strategy tends to look more like waiting for women to send me emails saying “I like your blog, would you like to go on a date?” which probably doesn’t generalize), but I’ve had many good interactions with Jake, and he has a beautiful family which means he must be doing something right. Also, Jake is poly, and I sometimes wonder if poly people are the only ones qualified to give dating advice: if you’re monogamous, you either met your future spouse quickly (in which case you have no experience), dated for years without meeting your spouse (in which case you can’t be very good), or aren’t looking for a committed relationship at all (which is just pickup artistry, and follows very different dynamics). Poly people are the only ones who can break out of this trilemma! 12: Christ And Counterfactuals is a blog on effective altruism from a Christian perspective. Some previous attempts at this have felt kind of forced, but the first post I read here was actually pretty interesting. Richard Swinburne (apparently “the world’s best Christian philosopher”), thinks that: “[One] reason why it is good that the human race should sometimes be in an initial situation of considerable ignorance about the causes and effects of our actions, is this. If God abolished the need for rational inquiry and gave us from childhood strong true beliefs about the causes of things, that would make it too easy for us to make moral decisions. As things are in the actual world, most moral decisions are decisions taken in uncertainty about the consequences of our actions. I do not know for certain that if I smoke, I will get cancer; or that if I do not give money to some charity, people will starve. So we have to make our moral decisions on the basis of how probable it is that our actions will have various outcomes—how probable it is that I will get cancer if I continue to smoke (when I would not otherwise get cancer), or that someone will starve if I do not give. Since probabilities are so hard to assess, it is all too easy to persuade yourself that it is worth taking the chance that no harm will result from the less demanding decision (the decision which you have a strong desire to make). And even if you face up to a correct assessment of the probabilities, true dedication to the good is shown by doing the act which, although it is probably the best action, may have no good consequences at all.” (Could a Good God Permit so Much Suffering? A Debate, pp. 52-53.) This is pretty galaxy-brained, but something galaxy-brained must be going on for God to tolerate the existence of evil at all, and this is a surprisingly natural extension of some common premises on the subject. 13: Swedish study: diagnosing the marginal patient with a psychiatric condition makes their life worse. Of the two mechanisms they looked at, stigma seems more involved than drug side effects. My opinion: this study was done on conscripts undergoing a mandatory psych evaluation for the army, who had no previous reason to think they had a psych disease and had not sought treatment. This is a different situation from somebody who comes to a psychiatrist asking for relief from specific symptoms they have noticed. Also, Sweden c. 2005 is a different culture from America 2025 in terms of how much stigma a psych diagnosis carries. I think it’s possible that if you never considered that you had psychiatric problems, and were suddenly given a diagnosis in 2005 Sweden and told you couldn’t serve in the army, that’s likely to destabilize your self-image more than a person who knows they’re depressed going to a psychiatrist in 2025 US and getting antidepressants. 14: RIP Felix Hill, research scientist at DeepMind and mentor to many in the AI community. You can read his suicide note here, though the obvious content warning applies. He says he took ketamine for mild anxiety and it plunged him into an incredibly deep depression that he couldn’t get out of; he leaves his story behind as a warning for others. I appreciate his warning, but I wish he had said more about what dose he used; different people’s ketamine doses vary by almost two orders of magnitude, I’d previously thought that the low doses were pretty safe and the high doses were sketchy, and I would like to know whether I should update or not. 15: RIP Max Chiswick, professional poker player, effective altruist, and ACX reader. 16: Adrian Dittman, a Twitter account widely accused of being Elon Musk’s alt, has been revealed to be . . . a guy named Adrian Dittman. Congrats to Maia Crimew and the Spectator for actually investigating this, unlike many other news sources which spread the Musk conspiracy theory. Also, the people involved got banned from X for some reason, maybe because this qualified as doxxing Dittman. 17: Related: Musk claims to be among the top players in the world at several computer games. A veteran Path of Exile gamer presents evidence that Musk faked his PoE2 accomplishments by hiring a Chinese guy to play on his account. Some Musk supporters in the comments suggest that maybe he hires the Chinese guy to level up his account, but his accomplishments (eg speedruns) are still his own? 18: Related: Sam Harris says he has been friends with Musk since 2008, but he noticed a sudden shift for the worse in his personality around 2020 which made it impossible to stay friends with him. He gives the example of Musk losing a bet with him that there would be 35,000+ COVID cases in the US, refusing to pay up, and launching personal attacks on Sam when asked to do so. What happened? Some theories: Musk turned right-wing, which ended his friendship with Sam for the same reason political differences have always ended friendships (but then what about the bet, which seems like objectively bad behavior?)
Inline links: this, The Case For Clinical Trial Abundance, NYT article calculating your chance of winning the lottery, here, @venturetwins, this year’s results are in, Gary Marcus and Miles Brundage have made a bet about AI progress, @tamaybes, by my estimation, Recursive Adaptation, my post on, the FDA tried to declare, will continue to prescribe, a blog on dating advice, Christ And Counterfactuals, the first post I read here, diagnosing the marginal patient with a psychiatric condition makes their life worse, RIP, here, RIP, a guy named Adrian Dittman, got banned from X for some reason, presents evidence
The Ozempocalypse Is Nigh
March 12, 2025 · Original source
Tirzepatide (Mounjaro®, Zepbound®)
Liraglutide (Victoza®, Saxenda®) …but liraglutide is noticeably worse than the others, and most people prefer either semaglutide or tirzepatide. These cost about $1000/month and are rarely covered by insurance, putting them out of reach for most Americans. …if you buy them from the pharma companies, like a chump. For the past three years, there’s been a shortage of these drugs. FDA regulations say that during a shortage, it’s semi-legal for compounding pharmacies to provide medications without getting the patent-holders’ permission. In practice, that means they get cheap peptides from China, do some minimal safety testing in house, and sell them online. So for the past three years, telehealth startups working with compounding pharmacies have sold these drugs for about $200/month. Over two million Americans have made use of this loophole to get weight loss drugs for cheap. But there was always a looming question - what happens when the shortage ends? Many people have to stay on GLP-1 drugs permanently, or else they risk regaining their lost weight. But many can’t afford $1000/month. What happens to them? Now we’ll find out. At the end of last year, the FDA declared the shortage over. The compounding pharmacies appealed the decision, but the FDA recently confirmed its decision is final. As of March 19 (for tirzepatide) and April 22 (for semaglutide), compounding pharmacies can no longer sell cheap GLP-1 drugs. Let’s take a second to think of the real victims here: telehealth company stockholders. Some compounding pharmacies are already telling their customers to look elsewhere, but not everyone is going gently into the good night. I’m seeing telehealth companies float absolutely amazing medicolegal theories, like: Compounding pharmacies are allowed to provide patients with a drug if they can’t tolerate the commercially available doses and need a special compounding dose. Perhaps our patients who were previously on semaglutide 0.5 mg now need, uh, semaglutide 0.51 mg. In fact, they need exactly 0.51 mg or they’ll die! Since the pharma companies don’t make 0.51 mg doses, it has to be compounded and we can still sell it.
Inline links: semi-legal, two million, confirmed, https://substackcdn.com/image/fetch/$s_!kj-h!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2Fa3d72e48-2e7b-4380-b461-349e799f03f6_616x471.png
But the compounders aren’t the only ones boxing clever. Novo Nordisk and Eli Lilly, the pharma companies behind semaglutide and tirzepatide respectively, have opened consumer-facing businesses about halfway between a traditional doctor’s appointment and the telehealth/compounder model that’s getting banned. So for example, Lilly Direct offers to “find you a doctor” (I think this means you do telehealth with an Eli Lilly stooge who always gives you the meds you want) and “get medications delivered directly to you”. The price depends on dose, but an average dose would be about $500 - so about halfway between the cheap compounding price and the usual insurance price. Not bad.
Inline links: Lilly Direct