Astral Codex Ten

GLP-1

15 min read

GLP-1

Article

GLP-1 is a recurring concept in the Astral Codex Ten archive, appearing 4 times across 4 issues between August 13, 2024 and March 12, 2025. The archive places it in contexts such as “means the intestine releases much more GLP-1”; “GLP-1 suggests maybe this was originally a food reward system”; “researchers found two separate behavioral effects of GLP-1. First, it made rats eat less”. It most often appears alongside FDA, Ozempic, China.

Metadata

  • Category: Concepts
  • Mention count: 4
  • Issue count: 4
  • First seen: August 13, 2024
  • 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.

Why Does Ozempic Cure All Diseases?
August 13, 2024 · Original source
If you want to learn more about GLP-1 receptor agonists and addiction, including the application to public policy, I highly recommend the Recursive Adaptation blog.
Inline links: Recursive Adaptation
GLP-1 Receptor Agonists: A New Treatment in Parkinson’s Disease gives us this diagram:
Inline links: GLP-1 Receptor Agonists: A New Treatment in Parkinson’s Disease
Sex is the other extremely-rewarding, sometimes-addictive behavior old enough that it might have shaped the evolution of the reward system. Do GLP-1 receptor agonists lower libido? Mouse studies say maybe, but human studies say no. A very straightforward extrapolation of the Skibicka result might suggest that GLP-1 drugs shouldn’t change libido overall, but should make people less intensely prefer good sex to bad sex. So far nobody has managed to get that study premise past an IRB, sorry.
Inline links: maybe, no
The Compounding Loophole
August 22, 2024 · Original source
I’m pretty encouraged by it. Not only does it provide GLP-1 drugs for a quarter of the price, but also people were really worried that diabetics wouldn’t be able to get their diabetes drugs because dieters would grab them off the shelf first. But now there’s more than enough GLP-1 agonists for everybody. This dramatically demonstrates how drug shortages are mostly regulatory problems (Adderall users, take note!)
…and they’re now the most valuable company in Europe. So they can probably eat the loss. What happens when the shortage ends? Compounding pharmacies are only allowed to do this because of a law that suspends some drug regulations during a “shortage”, ie when the drug is on the FDA’s drug shortage list. At some point, Novo Nordisk will build enough factories to meet capacity and there won’t be a shortage anymore. What then? Will the fun be over? Will GLP-1 agonists go back to costing $1,200/month again? Will most of the current users have to stop the drug and regain the lost weight? This would make tens of thousands of people really mad. I don’t know if the FDA has the guts to offend that many people. Their style is more to crush drugs before they ever come out, before anyone knows what they’re missing. During COVID, the DEA said that telemedicine was allowed to be cheap and convenient so patients could get care during lockdown. After the pandemic died down, they tried making it hard and expensive again, but so many patients protested that they backed off. The uproar we’ll get if the FDA tries to make GLP-1 drugs expensive again will make that one look like a tempest in a teapot. But Big Pharma will be even angrier if they don’t. And besides, they can’t keep the drug on their shortage list if everyone knows there’s no shortage. I really don’t know what will happen, and I don’t envy whichever FDA official is in charge of setting a policy on this. I did see one proposed solution somewhere or other (sorry if it’s yours and I’m not crediting you). Compound pharmacies are always allowed to make compounded medications for specific patients who have a “medical necessity” for a non-FDA-approved product. So in theory, you could try something like: Tell the patient to say that Ozempic causes them nausea.
Inline links: the most valuable company in Europe, they tried making it hard and expensive again
Now that we’ve gone over the pharmacology of the GLP-1 agonists, let’s get back to the economics.
Inline links: the pharmacology of the GLP-1 agonists
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
Three GLP-1 drugs are approved for weight loss in the United States:
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
Some people are stocking up. GLP-1 drugs keep pretty well in a fridge for at least a year. If you sign up for four GLP-1 telehealth compounding companies simultaneously and order three months from each, then you can get twelve months of medication. Maybe in twelve months the FDA will change their mind, or the pharmacies’ insane legal strategies will pay off, or Trump will invade Denmark over Greenland and seize the Novo Nordisk patents as spoils of war, or someone will finally figure out a diet that works.