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Notes -
Ever since the halcyon days of early 2020, where some yahoo dared us rationalist corona panickers to buy puts on cruise companies, I’ve been trying to recreate this missed opportunity (turns out, it wasn’t priced in).
Ozempic’s been getting a lot of good press in rat circles. Leaps calls on novo nordisk/eli lily?
I think eventually that these kinds of drugs will be shown to have extremely negative consequences for anyone who’s not extremely morbidly obese (or at least in bad enough shape that the side effects are less serious than the obesity). Of particular concern is the number of people who are using this product for aesthetic reasons rather than as medically necessary treatment. Women have used this stuff to fit in their wedding dresses as an example.
Long term, given that this substance acts like a hormone, I think that homeostasis will eventually strike leading to the body becoming less sensitive to semiglutide and therefore the person cannot feel full. And there have been some reports of things like stomach and intestinal issues, so I’m not sure about that either.
There have been lots of these pills in the past starting with fenfen in the 1990s. Most of them overhyped or have serious side effects (fenfen worked, but since it was basically an amphetamine, it caused a lot of heart problems and was withdrawn). The thing I keep coming back to is that people are so desperate for something like a skinny pill to be true that the public and doctors pounce on it without thinking about the long term effects. So that’s why I’m shorting it. I’m expecting wrongful death or serious injury lawsuits to kill it in all but the most serious cases and thus limit the profit from it.
Man, I genuinely do not understand the intuition that drives people to think that there must be a catch to Ozempic. You are doing better by couching your claim in terms of likelihood, but even then, I think this is misguided.
The universe is cold and uncaring, but it isn't actively malevolent. There is no law of physics that demands some kind of equivalent exchange here. Sometimes we just get lucky.
Biology has homeostasis, but homeostasis can break, and it can also be reset.
What drives such a belief? Do you think that drugs care about the moral pulchritude of those taking them? We discovered semaglutide in the saliva of Gila Monsters, which aren't known to be particularly discerning moral actors.
If someone with high blood pressure takes antihypertensives, their blood pressure falls. If someone with a normal BP takes them, theirs falls too. I would obviously prescribe them to the first case, and not the other two (at least for the control of blood pressure), but the mechanism remains the same.
This is a reasonable concern, but I think it might misinterpret what homeostasis is trying to do in obesity. The obese state isn't a healthy, well-regulated system that semaglutide is mischievously disrupting. For many people with obesity, the homeostatic system is already broken. Their bodies are defending a pathologically high set point for weight, ignoring satiety signals that should be firing, and managing insulin poorly.
Think of it less like a functioning thermostat that you're tricking, and more like a thermostat that's already broken and stuck at 90 degrees (Fahrenheit, I hope, if that's Celsius then turn off the oven) . The house is sweltering, the air conditioner is running itself ragged, and the occupants are miserable. Semaglutide comes along, and it isn't just put a bag of ice placed on the temperature sensor to fool it. It seems to actually repair the sensor.
If I hadn't been awake for 48 hours, I might have linked to a recent paper that semaglutide reduces the risk of Alzheimer's by 50% even in people without diabetes. You can look that up. You might even simply read Scott's deep dive on the topic.
Semaglutide is a miracle. Such mundane miracles are rare, but they do happen. Penicillin was quasi-miraculous, but even in this age of people sweating bullets about super-bugs, antibiotics save far more lives directly than they take.
I don't know about the advisability of taking the long on your short, but I'd probably benefit from taking the opposite end of a normal bet instead of trying to convince you. I strongly expect to make money on that 1:1 exchange if that were somehow feasible.
The drugs don’t care about morality, and I don’t see it as immoral to want to fit into a wedding dress. But if it comes to light that there are serious side effects, then the FDA is going to tighten the regulations on who can be prescribed the drug because a 19 year old trying to lose 20 pounds to fit in a dress should not be taking drugs that have serious side effects that far outweigh any benefits she gets from losing those 20 lbs. if she ends up with a permanent injury to her digestive tract, or a heart condition or something along those lines, it’s tragic.
Such risks might be worth taking if the person in question is obese enough to have the choice of risking those problems or dying if they don’t lose 200 pounds. We do that all tge time with other problems. My grandmother was on blood pressure medication that was slowly making her blind. The alternative was she has a heart attack. Blindness is bad, obviously, but when compared to a heart attack, not intolerable.
Yes, and having blood pressure go too low is dangerous in its own right. This is why I don’t think it’s going to be prescribed as often as people think. The use case depends on how bad the person’s obesity is, both in absolute weight and in the difficulty of losing tge weight. Depending on the costs it might be much lower than what people are expecting. And as such I think touting ozempic as a miracle cure for obesity is vastly overselling it.
My expectation is that ozempic will mostly be a last resort drug used much like gastric bypass surgery is today — reserved for serious cases of morbid obesity.
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How antibiotics take lives, except allergic reactions and antibiotics overuse/misuse reducing their effectiveness?
Overuse or misuse of antibiotics can lead to antibiotic-resistant infections, which can spread to people who weren't even on said antibiotic. They can ruin the natural balance of the gut microbiome, causing Clostridium difficile infections. As you've mentioned, some unfortunate souls get nasty allergic reactions which can kill them from the anaphylactic shock. I'm talking about all the ways they can cause harm, with no carve outs.
Edit: They can also be hepatic enzyme induces or inhibitors. If not planned for, this can cause overdoses or underdoses of seemingly unrelated drugs.
My mom found out she was allergic to penicillin as a little girl, when she had anaphylaxis. Fortunately she was ok and it hasn’t affected her life much.
But also yeah, antibiotic side effects can be real. It beats pneumonia, but uncontrollable diarrhea and stomach upset isn’t fun. Took me a while before I was back to normal.
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oh, I forgot that one, thanks!
and was not aware at all of that, double thanks!
I tried to cover this with "overuse/misuse reducing their effectiveness"
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Well, the lipostat theory would suggest that the obese already suffer from disrupted homeostasis via leptin resistance. Under that paradigm, GLP-1s are more akin to insulin for diabetics than more tolerance-building substances.
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Good point. All the hyped anti-aging drugs haven’t panned out either. Because things very very rarely do, and it’s good to always keep in mind that nothing ever happens. I hadn’t really considered it here, because like most rats/transhumanists I tend to pattern-match every criticism of ozempic, or of a hypothetical anti-aging drug, with a kind of moralising, small-minded complaint - ‘it’s the easy way out’ , ‘it’s unauthentic thinness’, ‘aging/dying is a part of life’ etc – I immediately dismiss.
I’m not going to say it’s impossible that this one is the one, but I think as far as putting money down, I’d wait a year or so to see if the hype is just hype or if it’s real, or if there’s not going to be issues with side effects making the product only “worth the risk” for people who are either going to lose several hundred pounds or die. If the product is only going to be used on the population of people who weigh 300+ lbs, that’s a much smaller customer base than if it can be used by every woman looking to lose ten pounds to fit a swimsuit or wedding dress. If it’s just morbid obesity, it’s life changing for those people, but I don’t think it’s something that’s going to spike the stock price like if you cured a common and deadly disease like cancer
There are a LOT of morbidly obese people. This would still be a major customer base.
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