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"No free lunch" is a reasonable question to ask when evaluating medication, if it would improve the evolutionary fitness of the majority of people. I think this

by strken 1y ago

"No free lunch" is a reasonable question to ask when evaluating medication, if it would improve the evolutionary fitness of the majority of people. I think this is behind some of the skepticism. If Ozempic is so great then how come our bodies don't just produce more GLP-1? How come we aren't like chimps, with eternally shredded bodies and cheese grater abs, provided we get the protein to support them? I would guess that getting fat in times of plenty was a feature and not a bug in the ancestral environment, and that's why we get fat today, which is obvious if you think about it. Still, it means GLP-1 agonists are smacking into quick "is it bullshit?" heuristics for a lot of people. The second point I haven't seen discussed is that weight loss drugs prior to GLP-1 agonists include cigarettes, which (worst case) give you cancer; stimulants, which cause your heart to fail; parasitic intestinal worms, which can kill you but more importantly are just plain gross; and mitochondrial uncouplers, which set you on fire at a cellular level. That's a long history of miracle weight loss drugs which turn out to have horrible side effects. It's not reasonable to think GLP-1 is bad just because of other drugs with different mechanisms, but it certainly causes some skepticism anyway.

rbranson 1y ago
none of the things you cited are “miracle weight loss drugs.” they are things people did to lose weight. these are the first class of drugs that actually cause people to lose weight.
- strken 1y ago
  I would have to check my sources but I'm pretty sure some of them have been prescribed for weight loss at various times. DNP and stimulants I'm more confident of, nicotine and tape worms I'm a bit iffy about.
  - King-Aaron 1y ago
    The American Tobacco Company marketed cigarettes for women's weight control in the 1920's. Lucky Strikes 'Reach for a Lucky" campaign was a big example of this as well, although they marketed it as an appetite suppressant rather than simply a miracle weight loss cure.
    - cik 1y ago
      Keeping in theme, Ozempic specifically has already been marketed off label as an appetite suppressant, rather than a pure weight loss drug. That's a more modern construct in its brief history.
  - notpushkin 1y ago
    Technically, nicotine can be classified as a stimulant: https://web.archive.org/web/20250712041104/https://psychonautwiki.org/wiki/Nicotine https://web.archive.org/web/20250712041104/https://psychonau...
    - eru 1y ago
      It's not a straight-up stimulant. It's complicated.
      - skeezyboy 1y ago
        cognitive stimulant definitely
        eru 1y ago
        There are some technical definition of what makes a stimulant a stimulant. It doesn't just have to have a vague stimulating effect. It's definitely a stimulant in colloquial English, just not in pharmacology.
  - mtlmtlmtlmtl 1y ago
    Amphetamine is actually a very effective weight loss drug. And it's sort of orthogonal to the fact that it's a stimulant. Stimulants in general can cause an acute reduction in appetite and temporary weight loss. This tends to stabilise with tolerance, however. As someone with obesity and ADHD, thus was my experience with methylphenidate treatment. And I used to think the weight loss effects of amphetamine were analogous until recently. Amphetamine and methyphenidate(MPH) have very different ways of acting as stimulants. MPH is an inhibitor of the dopamine transporter(DAT) and the norepinehrine transporter(NET). These cross-membrane proteins essentially "suck up" the dopamine or norepinehrine after neurotransmission, thus regulating the effect. MPH inhibits this process, increasing the effect. This is called a norepinephrine/dopamine reuptake inhibitor(NDRI). Cocaine also works like this, as well as the antidepressant wellbutrin(bupropion). Amphetamine on the other hand, is a bit more complicated. It interacts with DAT/NET as well, as a substrate, actually passing through them into the neuron. Inside the neuron, it has a complex series of interactions with TAAR1, VMAT2, and ion concentrations, causing signaling cascades that lead to DAT reversal. Essentially, enzymes are activated that modify DAT in such a way that it pumps dopamine out of the neuron instead of sucking it up. How that happens is very complicated and beyond the scope of this comment, but amphetamine's activity at TAAR1 is an important contributor. As such, amphetamine is a norepinephrine-dopamine releasing agent(NDRA). Methamphetamine, MDMA, and cathinone(from khat) also work like this. Anyway, recently I was reading about TAAR1 and learned something new, namely that TAAR1, besides being and internal receptor in monoaminergic neurons, is also expressed in the pancreas, the duodenum, the stomach, and intestines and in these tissues, TAAR1 activation will increase release of GLP-1, PYY, and insulin, as well as slow gastric emptying. So in essence, there may be some pharmacological overlap between ozempic and amphetamine(I'm still looking for data on how significantly amphetamine reaches TAAR1 in these tissues, so unclear what the relevance is. But amohetamine is known to diffuse across cellular membranes, so it's likely there is an effect). Also interesting, amphetamine was recently approved as a treatment for binge eating disorder. Not only because it causes weight loss, but because it improves functioning in the prefrontal cortex(crucial to its efficacy in ADHD), which is apparently implicated in the neuropsychological aspects of BED as well.
    - Fluorescence 1y ago
      > treatment for binge eating disorder There is a mixed picture on this. I see a lot reports of reports of it causing binging in the evenings despite no prior issues. The issue is that therapeutic doses are not the multi-day bender of a speed-freak that forgoes sleep to keep their blood-concentration permanently high. Instead it's a medicated window of 6-12 hours with a third or more of their waking hours remaining for rebound effects to unleash stimulation-seeking demons that run wilder than ever.
  - eru 1y ago
    Nicotine and caffeine have very well known appetite suppressing effects.
throwup238 1y ago
> How come we aren't like chimps, with eternally shredded bodies and cheese grater abs, provided we get the protein to support them? There are several reasons: Chimps have a higher density of testosterone receptors with a higher sensitivity than humans. Compared to humans, they are essentially roided out all the time. Humans are also hairless endurance hunters so we naturally have much larger fat reserves (15-25% of body weight vs <10% for chimps) in order to retain body heat and have enough energy to hunt prey till they collapse from exhaustion.
- mnky9800n 1y ago
  We also live on average more than twice as long as the average chimpanzee.
  - wiseowise 1y ago
    And average human isn’t spending as much time exercising as chimp does.
    - nickserv 1y ago
      And when we did our average lifespan was much shorter. Time to burn that Gym membership :-p
- cyrillite 1y ago
  Not to mention that we really are much more similar to chimps than they’re giving us credit for. If we ate a relatively low calorie, high protein diet, and maintained an active lifestyle, we’d all be pretty damn muscular and lean. Not roided out muscular, but far more so than I think the average person expects. Our body composition is significantly determined by relatively near-zero fitness demands in modern life and an overabundance of the wrong kinds of calories
  - b112 1y ago
    Yes just 150+ years ago most field work was done by hand, including moving rocks from fields, plowing with an animal (and a lot of human strength too). Just clearing new roads was mostly manual work. (Sure, you could blow up things, but then you still had to clear the bits and level the road. Yes horses existed, but mostly it was just people.) Every activity took more physical effort, everything was maintained manually. Even if you were a bookkeeper, it was all hand written, and any math was with a slide rule or on paper, or in your head. It takes more calories to move a slide rule than work a calculator, more to write than type. And all the while, the muscles of the arm, and the upper body are being used as you press against that paper. Moving over a page meant arm and shoulder and back and more got a bit of workout. Every little bit added up. Now we often type without moving our upper arms or shoulders. Without a change in back or upper torso movement. It takes more calories to read than just sit still, more calories to think deeply than not. Even going to the bathroom meant putting on boots and coat, and walking to the outhouse. We're immensely lazy today as a peoples.
wraptile 1y ago
> If Ozempic is so great then how come our bodies don't just produce more GLP-1 This strays too far into appeal to nature teritory. Evolution made us fit to reproduce not to age. As for "no free lunch" - we do have a lot of that in medicine historically speaking: iodine salt, clean water, vitamins (C, D), iron supplements, hormone theraphy, vaccines. The field of medicine is no stranger to free lunch.
- lazeythrowerb 1y ago
  Exactly! Further for evolution in the larger picture, it is actually necessary for living beings to die at some point, because of overpopulation. Survival instinct of the individual is only necessary to achieve enough reproduction. Death after reproduction age is necessary for evolution.
- strken 1y ago
  By "no free lunch" I meant that any change which evolution could easily have led to, but didn't, has likely not been evolutionarily advantageous for long enough or with great enough selective pressure to happen. Emphasis on "easily", "likely", and "long enough"/"great enough". I don't think evolution could easily have solved most dietary deficits, manufactured clean water, prevented every endocrine condition, or designed vaccines for us. I'm not even sure what that last one would mean! These things are a nearly-free lunch because we live in industrial economies that can ship oranges around the world and build dams, but they're not an evolutionary free lunch. (And the loss of vitamin C production is argued to be an adaptation to starvation, too, just like we're arguing that lower GLP-1 is an adaptation to starvation: https://academic.oup.com/emph/article/2019/1/221/5556105 https://academic.oup.com/emph/article/2019/1/221/5556105)
b800h 1y ago
The other side of this is related to morals. People learned self-discipline by having to moderate their diet. Replacing that challenge with an injection is another example of a world in which people are not challenged to grow as people, but merely go out and buy something to make themselves feel or look better.
- Llamamoe 1y ago
  Honestly, this is essentially BS. I'd say that 95% of healthy weight people stay that weight because their metabolism and appetite works properly. People who stay in shape by paying careful attention to their diet are a tiny minority.
  - jahsome 1y ago
    What information do you have to back up this claim?
    - ddorian43 1y ago
      Eh, most people just wing it at everything. Including diet. Source: have to do keto diet and be strict to stop food addiction.
  - boredhedgehog 1y ago
    It only takes one man to prove that it's possible. That makes it a moral matter.
  - aerhardt 1y ago
    Where I live (Spain) there’s a massive intergenerational gap between how our parents ate and how we eat and exercise. A huge number of people around me go to great lengths to control what they eat and make an effort to move. I see it at the beach, at the restaurant or at the gym. You can ask anyone in the older generations if younger people are physically healthier and you’d find an almost unanimous yes. Coincidentally we have one of the highest life expectancies in the world. None of this is given.
WithinReason 1y ago
> If Ozempic is so great then how come our bodies don't just produce more GLP-1? To store calories so you don't starve. This is a failure mode of evolution and there is in fact "free lunch" when we use technology to reoptimise our bodies to calorie abundance
- skeezyboy 1y ago
  > when we use technology to reoptimise our bodies to calorie abundance replace "calorie abundance" with "sedentary lifestyle" and youre there. its people eating more than they burn off because they dont exert themselves because thats what being an adult means.
  - deleted 1y ago
    [deleted]
  - BigJ1211 1y ago
    Calorie abundance is accurate too, food has never been as cheap and delicious as it is now. Not to mention the ultra-processed high-density foods we have now. Meaning you can easily overeat with an active lifestyle too. In fact we have entire sports in which it's beneficial to do so. (Rugby/American Football, Strongman competitions and Sumo wrestling to name a few obvious ones)
    - Damogran6 1y ago
      Not just delicious...dangerously, addictively, delicious. I don't by Doritos because for me, any size bag is one serving. On Zepbound and it's stunning how my favorite beer...the one I craved and tasted so good 'why don't I have another?'...no longer has a hold on me. I could take two or three sips, set it down, and walk away. I also now feel full, but not disgustingly over-stuffed now.
  - guerrilla 1y ago
    You can't outrun a bad diet. You can easily out-eat any exercise though. Check just how few calories stationary cycling for an hour burns. I can eat that many calories in 5 minutes.
Nesco 1y ago
I am pretty sure uncouplers will make a come back. Just something a little more targeted and safer than good ol’ DNP
- nkmnz 1y ago
  looking for this, hu? https://en.wikipedia.org/wiki/HU6 https://en.wikipedia.org/wiki/HU6
  - Nesco 1y ago
    Yes, but also BAM15 and mRNA based UCPs overexpression Longer term if it works more research in the domain, including variations of the other well known ones (DNP, XCT-790, mitoCCCP, …) I firmly believe that combined with: - additional progress on the current targets (GLP-1, GIP, …) - compounds to counteracts muscle loss like myostatin inhibitors - food options being shaped by more health conscious consumers Having a slow metabolism will stop being an disadvantage by midcentury
- loeg 1y ago
  But why? Ozempic et al solve the input end of the equation. Burning more and literally being warmer isn't better.
  - cthalupa 1y ago
    I would agree, personally - I won't go near DNP, and even the newer stuff like BAM15 that is supposed to be incredibly selective I am quite suspicious of. But you still see people losing tons of weight on GLP-1s wanting it to go faster, drop more pounds, etc. I'm a big proponent of them - and I have enough risk tolerance that I'm on grey market retatrutide - but I see a lot of people that want to just keep adding more and more chemicals to the equation to solve the issue. I've taken the time to significantly modify my food and exercise habits, and believe that I'll be able to maintain my weight loss if I were to go off of the GLP-1. But a lot of people haven't. They eat the same bad food, just in lower quantities, don't increase their protein and fiber intake, don't exercise, and just up the dose or add a new compound when their rate of weight loss doesn't satisfy them. There's tons of interest in BAM15, clenbuterol, and all sorts of experimental substances. Tons of people taking things like tesamorelin and ipamorelin too. I think the GLP-1s are basically miracle drugs that have allowed a lot of people, including myself, to totally revamp their approaches to diet and fitness. But there's a lot of people that are going to be more than happy to increase their cocktail with anything they think will get them skinny faster.
jxf 1y ago
> If Ozempic is so great then how come our bodies don't just produce more GLP-1? We don't know. But one early signal is that you lose an atypical combination of muscle mass and not just fat, which is not a good evolutionary adaptation if you are an endurance hunter. https://healthcare.utah.edu/newsroom/news/2025/08/new-study-raises-questions-about-how-ozempic-affects-muscle-size-and-strength https://healthcare.utah.edu/newsroom/news/2025/08/new-study-...
- Nursie 1y ago
  Muscle-mass loss is normal on any weight-losing diet, and the link says it is actually less than expected…
eru 1y ago
> The second point I haven't seen discussed is that weight loss drugs prior to GLP-1 agonists include cigarettes, which (worst case) give you cancer; [...] Nicotine works just fine as an appetite suppressant without the carcinogenic tar you get from burning tobacco leaves. Similar for other stimulants or stimulant-like substances. But I agree that they get a bad reputation, despite actually working pretty well, and with manageable side-effects: not worse than what I've heard about the nausea people get on GLP-1 drugs, and much better than the health effects of obesity.
- loeg 1y ago
  YMMV but personally I did not find nicotine an effective appetite suppressant.
- Telemakhos 1y ago
  Nicotine, even without the tar, reduces your nitric oxide levels leading to vasoconstriction, damages endothelial health, and can lead to atherosclerosis. You're much better off eating less and making more time to exercise instead of ingesting foreign substances to compensate for bad habits.
  - eru 1y ago
    Compare and contrast https://gwern.net/nicotine https://gwern.net/nicotine
benchly 1y ago
> If Ozempic is so great, how come our bodies don't just... While I agree with your sentiment, your argument here assumes the human body always makes intelligent decisions for itself. My obstructive sleep apnea would like a word. After it's done choking me awake, of course. The body is a marvelous machine, but it is far from a perfect or intelligent design. We are lucky to have what we have, but expect operating mistakes.
- wisty 1y ago
  Evolution should make intelligent choices for us but there's thousands years where a few extra pounds meant surviving a famine. Also I bet it will kill a few people with eating disorders. As long as you're in a 1st world country and have a BMI over ... maybe 25 (and aren't on steroids so you're both anorexic and overweight at the same time) I'd guess you're dodging a lot of the most obvious risks.
  - benchly 1y ago
    How do you define 'intelligent' and 'evolution?' I think we might differ on what those words mean, which would make this conversation difficult, so let's clarify where each of us is coming from. My understanding (which may be slightly misguided because this is definitely not my field) is that Intelligence is the ability to use information for reasoning, decision making and achieving understanding. This ability, as a directed action, only applies to creatures with consciousness. Regarding evolution, my understanding is closer to a process that is more akin to a passive filter, with no guidance to speak of unless we want to stretch the limits of the concept of guidance to encompass survival, which is the genetic materials of those who survive the environment getting passed on, which would also implies that sometimes garbage/noise stays in the gene pool. While information (genetic material) is being passed on, it is not being selected through reasoning or consideration, but more of a mechanical process (although there's an argument to be had that we, humans, might be changing that game). How would you define those words? Happy to consider understanding different than my own, since I do find it interesting.
    - wisty 1y ago
highfrequency 1y ago
"No free lunch" is not good intuition for many biological processes. There has been near zero evolutionary pressure toward improvements that primarily manifest after age 60. Separately, evolution took place in a very energy and calorie constrained environment which is very dissimilar to today's world. Many people do not feel spontaneous desire to fast or run laps even though these are clearly beneficial.
Fargren 1y ago
> if it would improve the evolutionary fitness of the majority of people Evolution led to the intelligence that led to creating Ozempic. Maybe that's the mechanism by which evolution is improving evolutionary fitness. The idea that what was created by man is not part of evolution is part of the naturalism fallacy; it's the false belief that the domain of nature stops at the doors of the lab.
fnord77 1y ago
"no free lunch" usually boils down to violating some law of thermodynamics. since we're preventing the body from adding excess potential energy to the system, I don't think this is violating any no-free-lunch rules.
AngryData 1y ago
I agree with you overall, but humans atrophying muscle away so rapidly, and also building muscle so quickly, is fairly unique to humans so im not sure there has to be a downside to being shredded all the time like a gorilla through some sort of medical treatment in the future. We certainly haven't figured that out now, but I wouldn't be surprised if some gene therapy and chemical cocktail couldn't allow it safely someday. From everything ive seen it seems to be just a calorie saving adaptation so more energy can go to the brain. And perhaps make more varied and specialized living strategies, made possible thanks to our brain, more efficient by not supporting large muscle groups we don't always need. Of course maybe its not possible, but it is the default for pretty much every other animal so its not like it is trying something completely outrageous like trying to eliminate sleep.
lo_zamoyski 1y ago
> cheese grater abs Washboard abs?
jart 1y ago
It only makes sense if you understand that everyone is being poisoned, and this is the cure.
VeejayRampay 1y ago
that's not why we get fat we get fat because of the american diet, priori to which people in the world were actually not that fat the lack of fermented food, the epidemics of ultra-processed, ultra-rich and grotesquely fat and sugary food is why people have gotten fat, which is a relatively recent phenomenon (and which is not as widespread in culture that resist the American diet the most like the French and the Japanese)
wkat4242 1y ago
> If Ozempic is so great then how come our bodies don't just produce more GLP-1? Because our bodies have been tuned to deal with food shortages for hundreds of thousands of years. Now we live in an age of abundance but our bodies still try to harvest each calorie they can get. If this continues we might evolve to no longer store surplus calories as fat. Though I doubt it because the age people die from overweight related issues is way after the age most people have kids at. But I imagine that soon we will be able to directly tune some of that evolutionary bagage that no longer applies, by gene modification.
gniv 1y ago
This blog post by Derek Thompson answered a lot of questions for me: https://www.derekthompson.org/p/why-does-it-seem-like-glp-1-drugs https://www.derekthompson.org/p/why-does-it-seem-like-glp-1-... In particular it seems Ozempic has anti-inflamatory effects which could explain a lot of these non-weight-loss-related results.
tomrod 1y ago
> our bodies don't just produce more GLP-1 Dominant subgroups in a species are dominant because their parents survived that last set of pressures (external death inducements) at a higher rate than other subgroups -- but won't necessarily see the same results with the current set. Even 90 years ago, there was significant loss of life due to famine, so selection was towards people who could efficiently gain and store calories in a biological Keynesian strategy. Now we have the opposite problem -- abundance of life-sustaining food produced for cheap but good quality food is expensive (in the US -- many other parts of the world have their quality food cheaper but I digress). So there hasn't been enough pressure (external-induced death) for GLP-1. As a species with a remarkable ability to modify its environment to suit our purposes, body response to disease is just another thing to modify.
- FeloniousHam 1y ago
  > but good quality food is expensive (in the US -- many other parts of the world have their quality food cheaper but I digress Let's digress. I read this frequently in various forms on this forum, and it's always "just so" justification. My own heuristic thought is that "low quality" food (high energy, long shelf-life processed foods) is very cheap because it is produced at scale and can be stored, while "high quality" (fresh products) is not cheap for the opposite reason. The US has the cheapest food in the world [1]. Expensive food is expensive, but I would bet quality food is cheaper here than anywhere else. The "problem" is that when presented with a cheap, easy, tasty, high calorie food option against a relatively more expensive "quality" option, consumers choose the former because it's cheaper, easier, tastier, and provides more calories. I would bet this is even true when the absolute difference in price is small. [1] https://www.fastcompany.com/91208387/food-grocery-prices-us-world-comparison https://www.fastcompany.com/91208387/food-grocery-prices-us-...
  - tomrod 1y ago
    > Expensive food is expensive, but I would bet quality food is cheaper here than anywhere else. Having lived in a few other countries with less industrialized distribution networks, no, this claim is dramatically incorrect. Fruits, vegetables, staples like rice, and basic forms of protein (fish, insects and sea critters, some chicken) are much, much cheaper relative to processed foods. Larger protein sources like beef, pork, or bushmeat is relatively more expensive, however, unless you opt for poor quality processing like cheap "corned beef" made from offal. As an economist, I appreciate the difficulty of making apples-to-apples comparisons across countries for things like food prices, as even the acclaimed "Big Mac Index" assumes that a Big Mac has a similar relative status across countries (though the oft-misunderstood intent of the Big Mac Index is to more to compare consistent production costs). In some places a Big Mac is fancy, in the US it is considered fairly garbage but consistent. For example, in a market in the Philippines, you have mostly cash transactions and informal capture for what the majority of people purchase. The purchasing is done more in these almost farmers-market style transfer versus grocery stores in the US. They _do_ have grocery stories, but almost uniformly for processed food distribution versus fresh food in the markets. It's much cheaper to eat healthier from the markets and through the informal distribution network of sari-sari stores versus equivalent nutrition from processed food from the grocery stores. Also, consider the results of this recent study: https://arstechnica.com/health/2025/08/in-trial-people-lost-twice-as-much-weight-by-ditching-ultraprocessed-food/ https://arstechnica.com/health/2025/08/in-trial-people-lost-...
physPop 1y ago
Because over the course of a billion years of history, evolutionary pressures essentially end after child-rearing ages.
jghn 1y ago
> if it would improve the evolutionary fitness of the majority of people The issue with this logic is that evolution tends to find local, not global, maxima
sumeno 1y ago
If not having cancer is so great why don't our bodies just not make cancer cells? Weight loss aids are given far more scrutiny because people wrongly view it as a moral failing
- ifyoubuildit 1y ago
  As I understand it, species that are really good at healing from injuries are more likely to develop cancer. So evolution has to optimize for survival via healing vs survival via not getting cancer. Some people probably do come at it from the moral angle. But there are good reasons to assume that this time isn't different, that there is indeed no free lunch. Thankfully, everyone is free to make that risk assessment themselves. Just don't start trying to force it on anyone.
  - sumeno 1y ago
    It seems like you really missed the point. Of course there are reasons we still get cancer, just like there are reasons people get fat. Evolutionarily people are way more likely to die of being under nourished than over, so the body packs on fat when it can. Evolution did not optimize for 2025 > Some people probably do come at it from the moral angle. But there are good reasons to assume that this time isn't different, that there is indeed no free lunch. I'm struggling to understand what these sentences even mean. A medication may have side effects? Like every single medication we take? Yeah, of course it might. We don't have threads clutching their pearls about most medicines though. Tylenol can easily kill you if abused, but we don't have threads talking about how there's "no free lunch" for people using Tylenol responsibly. > Thankfully, everyone is free to make that risk assessment themselves. Just don't start trying to force it on anyone. Who is saying anything about forcing something on you? Is someone trying to force you to take Ozempic?
    - ifyoubuildit 1y ago
      > It seems like you really missed the point Yeah, I guess I don't really know what your point was if it wasn't to ask why we get cancer. Maybe that's my fault? > A medication may have side effects ... beyond the initially understood ones. Tylenol has been around for a long time. When it first came out, people were probably popping it like candy until they realized the limits, and now it's pretty well understood. And who cares if people are "clutching their pearls"? What harm does that do? > Is someone trying to force you to take Ozempic? Not yet, but I won't be surprised if people start pushing for it. Think about things like soda laws and seatbelt laws. If my being obese is costing you tax or insurance dollars and we have this magic pill, it's only a matter of time before the machine does its thing.
api 1y ago
Natural selection optimizes for long term survival of genes. Humans are probably long-lived because we have high maintenance offspring and a survival strategy built around communicating culture, but this only necessitates survival through 2-3 generations worth of time. Anything beyond that won't be selected for. Same with health, etc. A bio professor once said "life doesn't work perfectly, it just works." There's a lot left on the table because evolution optimizes for the median case over time.
paulcole 1y ago
If insulin is so great why does my pancreas simply not produce it?
JumpCrisscross 1y ago
> If Ozempic is so great then how come our bodies don't just produce more GLP-1? Idk, why can’t we synthesise vitamin C? Why do we have a bent oesophagus prone to choking and heads bigger than womena’ hips? We weren’t intelligently designed. To the degree we were optimised for anything it isn’t the modern environment. A lot of pushback against medicine in general seems to derive from an underlying belief in an innate perfection of human biology.
- fc417fc802 1y ago
  Both of your examples have no straightforward solution. Whereas we already have the mechanism in question so the question "why doesn't it just ramp up" is quite reasonable. Biology is a highly tuned system.
  - JumpCrisscross 1y ago
    > your examples have no straightforward solution In humans? No. In our ancestors and every other animal around us? Yes. > we already have the mechanism in question so the question "why doesn't it just ramp up" is quite reasonable Our species almost got wiped out in an ice age less than a hundred thousand years ago [1]. It's possible we had the ability to ramp up GLP-1, but that it got eliminated in a famine. [1] https://www.npr.org/sections/krulwich/2012/10/22/163397584/how-human-beings-almost-vanished-from-earth-in-70-000-b-c https://www.npr.org/sections/krulwich/2012/10/22/163397584/h...
    - fc417fc802 1y ago
      > In our ancestors and every other animal around us? Yes. Right so my point is, with no smooth optimization path towards X in a given species the question "why doesn't species just X" has a readily available answer - because biased random walks are fickle and the pathway likely convoluted. Whereas when a smooth optimization path is available it becomes reasonable to ask "then why isn't species doing X already"? Assuming a long enough timescale then there must be some selection pressure preventing it. I agree that the ice age is a reasonable hypothesis. If we were exposed to repeated boom-bust cycles of extended duration (ie multi-generational) then it's at least plausible that we gained some mechanism dedicated to preventing us from adapting in that direction. Still it's an entirely reasonable question that needs to be asked when considering the potential for serious side effects. If the hypothesis is that this is actively prevented for historical reasons then we should want to see the precise molecular mechanism hunted down in order to validate that. Keep in mind that an alternative hypothesis would take the general form that ramping it up causes serious deleterious side effects in the long term. It's quite like Chesterton's fence. There must be a reason so we would do well to understand approximately what that might be before tinkering.
random3 1y ago
I'm one of those watching on the side, wishing there would be a holistic, aggregated, view on all pros/cons that highlight each results statistical relevance as well (in particular it'd be great to understand test samples). On the natural evolution. I think it's best to think of it as a proces, with optimal state being a limit (e.g. in time, in total population), but especially in a changing environment. So, as it became easier to procure/produce fats or sugars there can be local sub-optimal states. So, in this framework, th "how come our bodies don't just produce more GLP-1?" question, can be answered with the fact that it's possible that we just haven't adapted yet. If we end up back to previous availability.— e.g. we lose farm land and "starve" again it would end up being the right evolutionary speed, if not, those that naturally produce more, may end up becomign majoritary. The bottom line is that natural evolution is a long term process that's adapting things to long term changes and "long" here can mean many generations. In a sense, philsophically, I wonder what prevents our own "changes" to be just a natural evolution of the natural evolution— i.e. a "conscious" evolution.
- dbliss 1y ago
  I always wondered if evolution through natural selection has essentially halted for humans for the most part. My thinking is even the previously most likely to die before child bearing has been reversed by modern society. Given that it happens at such a long time scale and modern humans and technology hasn't be around that long in the grand scheme of things it's probably not true, but I always found it interesting...
CyanLite2 1y ago
Our bodies haven’t evolved yet to produce more GLP-1 because until recently (~70 years ago) malnutrition and hunger had been one of the top killers of humans. Frankly put, we weren’t designed to live this long. We’re designed to consume calories and store those calories indefinitely to meet short term needs, rather than lifelong health. But we weren’t also designed to consume microplastics, artificial sweeteners, or flavors designed in a laboratory. Yet here we are. And it’s quite probable those things contribute to obesity.
42772827 1y ago
> If Ozempic is so great then how come our bodies don't just produce more GLP-1? How come we aren't like chimps, with eternally shredded bodies and cheese grater abs, provided we get the protein to support them? Evolution favored this level of GLP1, then we invented agriculture, and cooking, and bliss points. Now it’s far easier to ingest massive numbers of calories in ways that our old world systems can’t properly signal against. Evolution hasn’t caught up and maybe never will.
loeg 1y ago
> "No free lunch" is a reasonable question to ask when evaluating medication, if it would improve the evolutionary fitness of the majority of people. I think this is behind some of the skepticism. If Ozempic is so great then how come our bodies don't just produce more GLP-1? We can do science and technology on timescales vastly faster than evolution. "Why didn't evolution do it?" is just a very irrelevant question. > The second point I haven't seen discussed is that weight loss drugs prior to GLP-1 agonists include cigarettes, which (worst case) give you cancer; stimulants, which cause your heart to fail; parasitic intestinal worms, which can kill you but more importantly are just plain gross; and mitochondrial uncouplers, which set you on fire at a cellular level. That's a long history of miracle weight loss drugs which turn out to have horrible side effects. Cigarettes, parasitic worms, and 2,4-DNP were never medications.
- spauldo 1y ago
  Tobacco, and cigarettes in particular, has been used as a medicine for hundreds of years. And it's not just in the distant past - a friend of mine was actually prescribed cigarettes for anxiety about 30 years ago here in the US when he was 14. There are various health benefits to smoking, believe it or not. They're just outweighed by the downsides.
elzbardico 1y ago
"No free lunch" is a heuristic, a useful one most of the time, just that. But it is not a hard nature law such as the speed of light in vacuum.

by strken 1y ago

rbranson 1y ago

none of the things you cited are “miracle weight loss drugs.” they are things people did to lose weight. these are the first class of drugs that actually cause people to lose weight.

strken 1y ago
I would have to check my sources but I'm pretty sure some of them have been prescribed for weight loss at various times. DNP and stimulants I'm more confident of, nicotine and tape worms I'm a bit iffy about.
- King-Aaron 1y ago
  The American Tobacco Company marketed cigarettes for women's weight control in the 1920's. Lucky Strikes 'Reach for a Lucky" campaign was a big example of this as well, although they marketed it as an appetite suppressant rather than simply a miracle weight loss cure.
  - cik 1y ago
    Keeping in theme, Ozempic specifically has already been marketed off label as an appetite suppressant, rather than a pure weight loss drug. That's a more modern construct in its brief history.
- notpushkin 1y ago
  Technically, nicotine can be classified as a stimulant: https://web.archive.org/web/20250712041104/https://psychonautwiki.org/wiki/Nicotine https://web.archive.org/web/20250712041104/https://psychonau...
  - eru 1y ago
    It's not a straight-up stimulant. It's complicated.
    - skeezyboy 1y ago
      cognitive stimulant definitely
      - eru 1y ago
        There are some technical definition of what makes a stimulant a stimulant. It doesn't just have to have a vague stimulating effect. It's definitely a stimulant in colloquial English, just not in pharmacology.
- mtlmtlmtlmtl 1y ago
  Amphetamine is actually a very effective weight loss drug. And it's sort of orthogonal to the fact that it's a stimulant. Stimulants in general can cause an acute reduction in appetite and temporary weight loss. This tends to stabilise with tolerance, however. As someone with obesity and ADHD, thus was my experience with methylphenidate treatment. And I used to think the weight loss effects of amphetamine were analogous until recently. Amphetamine and methyphenidate(MPH) have very different ways of acting as stimulants. MPH is an inhibitor of the dopamine transporter(DAT) and the norepinehrine transporter(NET). These cross-membrane proteins essentially "suck up" the dopamine or norepinehrine after neurotransmission, thus regulating the effect. MPH inhibits this process, increasing the effect. This is called a norepinephrine/dopamine reuptake inhibitor(NDRI). Cocaine also works like this, as well as the antidepressant wellbutrin(bupropion). Amphetamine on the other hand, is a bit more complicated. It interacts with DAT/NET as well, as a substrate, actually passing through them into the neuron. Inside the neuron, it has a complex series of interactions with TAAR1, VMAT2, and ion concentrations, causing signaling cascades that lead to DAT reversal. Essentially, enzymes are activated that modify DAT in such a way that it pumps dopamine out of the neuron instead of sucking it up. How that happens is very complicated and beyond the scope of this comment, but amphetamine's activity at TAAR1 is an important contributor. As such, amphetamine is a norepinephrine-dopamine releasing agent(NDRA). Methamphetamine, MDMA, and cathinone(from khat) also work like this. Anyway, recently I was reading about TAAR1 and learned something new, namely that TAAR1, besides being and internal receptor in monoaminergic neurons, is also expressed in the pancreas, the duodenum, the stomach, and intestines and in these tissues, TAAR1 activation will increase release of GLP-1, PYY, and insulin, as well as slow gastric emptying. So in essence, there may be some pharmacological overlap between ozempic and amphetamine(I'm still looking for data on how significantly amphetamine reaches TAAR1 in these tissues, so unclear what the relevance is. But amohetamine is known to diffuse across cellular membranes, so it's likely there is an effect). Also interesting, amphetamine was recently approved as a treatment for binge eating disorder. Not only because it causes weight loss, but because it improves functioning in the prefrontal cortex(crucial to its efficacy in ADHD), which is apparently implicated in the neuropsychological aspects of BED as well.
  - Fluorescence 1y ago
    > treatment for binge eating disorder There is a mixed picture on this. I see a lot reports of reports of it causing binging in the evenings despite no prior issues. The issue is that therapeutic doses are not the multi-day bender of a speed-freak that forgoes sleep to keep their blood-concentration permanently high. Instead it's a medicated window of 6-12 hours with a third or more of their waking hours remaining for rebound effects to unleash stimulation-seeking demons that run wilder than ever.
- eru 1y ago
  Nicotine and caffeine have very well known appetite suppressing effects.

throwup238 1y ago

> How come we aren't like chimps, with eternally shredded bodies and cheese grater abs, provided we get the protein to support them? There are several reasons: Chimps have a higher density of testosterone receptors with a higher sensitivity than humans. Compared to humans, they are essentially roided out all the time. Humans are also hairless endurance hunters so we naturally have much larger fat reserves (15-25% of body weight vs <10% for chimps) in order to retain body heat and have enough energy to hunt prey till they collapse from exhaustion.

mnky9800n 1y ago
We also live on average more than twice as long as the average chimpanzee.
- wiseowise 1y ago
  And average human isn’t spending as much time exercising as chimp does.
  - nickserv 1y ago
    And when we did our average lifespan was much shorter. Time to burn that Gym membership :-p
cyrillite 1y ago
Not to mention that we really are much more similar to chimps than they’re giving us credit for. If we ate a relatively low calorie, high protein diet, and maintained an active lifestyle, we’d all be pretty damn muscular and lean. Not roided out muscular, but far more so than I think the average person expects. Our body composition is significantly determined by relatively near-zero fitness demands in modern life and an overabundance of the wrong kinds of calories
- b112 1y ago
  Yes just 150+ years ago most field work was done by hand, including moving rocks from fields, plowing with an animal (and a lot of human strength too). Just clearing new roads was mostly manual work. (Sure, you could blow up things, but then you still had to clear the bits and level the road. Yes horses existed, but mostly it was just people.) Every activity took more physical effort, everything was maintained manually. Even if you were a bookkeeper, it was all hand written, and any math was with a slide rule or on paper, or in your head. It takes more calories to move a slide rule than work a calculator, more to write than type. And all the while, the muscles of the arm, and the upper body are being used as you press against that paper. Moving over a page meant arm and shoulder and back and more got a bit of workout. Every little bit added up. Now we often type without moving our upper arms or shoulders. Without a change in back or upper torso movement. It takes more calories to read than just sit still, more calories to think deeply than not. Even going to the bathroom meant putting on boots and coat, and walking to the outhouse. We're immensely lazy today as a peoples.

wraptile 1y ago

> If Ozempic is so great then how come our bodies don't just produce more GLP-1 This strays too far into appeal to nature teritory. Evolution made us fit to reproduce not to age. As for "no free lunch" - we do have a lot of that in medicine historically speaking: iodine salt, clean water, vitamins (C, D), iron supplements, hormone theraphy, vaccines. The field of medicine is no stranger to free lunch.

lazeythrowerb 1y ago
Exactly! Further for evolution in the larger picture, it is actually necessary for living beings to die at some point, because of overpopulation. Survival instinct of the individual is only necessary to achieve enough reproduction. Death after reproduction age is necessary for evolution.
strken 1y ago
By "no free lunch" I meant that any change which evolution could easily have led to, but didn't, has likely not been evolutionarily advantageous for long enough or with great enough selective pressure to happen. Emphasis on "easily", "likely", and "long enough"/"great enough". I don't think evolution could easily have solved most dietary deficits, manufactured clean water, prevented every endocrine condition, or designed vaccines for us. I'm not even sure what that last one would mean! These things are a nearly-free lunch because we live in industrial economies that can ship oranges around the world and build dams, but they're not an evolutionary free lunch. (And the loss of vitamin C production is argued to be an adaptation to starvation, too, just like we're arguing that lower GLP-1 is an adaptation to starvation: https://academic.oup.com/emph/article/2019/1/221/5556105 https://academic.oup.com/emph/article/2019/1/221/5556105)

b800h 1y ago

The other side of this is related to morals. People learned self-discipline by having to moderate their diet. Replacing that challenge with an injection is another example of a world in which people are not challenged to grow as people, but merely go out and buy something to make themselves feel or look better.

Llamamoe 1y ago
Honestly, this is essentially BS. I'd say that 95% of healthy weight people stay that weight because their metabolism and appetite works properly. People who stay in shape by paying careful attention to their diet are a tiny minority.
- jahsome 1y ago
  What information do you have to back up this claim?
  - ddorian43 1y ago
    Eh, most people just wing it at everything. Including diet. Source: have to do keto diet and be strict to stop food addiction.
- boredhedgehog 1y ago
  It only takes one man to prove that it's possible. That makes it a moral matter.
- aerhardt 1y ago
  Where I live (Spain) there’s a massive intergenerational gap between how our parents ate and how we eat and exercise. A huge number of people around me go to great lengths to control what they eat and make an effort to move. I see it at the beach, at the restaurant or at the gym. You can ask anyone in the older generations if younger people are physically healthier and you’d find an almost unanimous yes. Coincidentally we have one of the highest life expectancies in the world. None of this is given.

WithinReason 1y ago

> If Ozempic is so great then how come our bodies don't just produce more GLP-1? To store calories so you don't starve. This is a failure mode of evolution and there is in fact "free lunch" when we use technology to reoptimise our bodies to calorie abundance

skeezyboy 1y ago
> when we use technology to reoptimise our bodies to calorie abundance replace "calorie abundance" with "sedentary lifestyle" and youre there. its people eating more than they burn off because they dont exert themselves because thats what being an adult means.
- deleted 1y ago
  [deleted]
- BigJ1211 1y ago
  Calorie abundance is accurate too, food has never been as cheap and delicious as it is now. Not to mention the ultra-processed high-density foods we have now. Meaning you can easily overeat with an active lifestyle too. In fact we have entire sports in which it's beneficial to do so. (Rugby/American Football, Strongman competitions and Sumo wrestling to name a few obvious ones)
  - Damogran6 1y ago
    Not just delicious...dangerously, addictively, delicious. I don't by Doritos because for me, any size bag is one serving. On Zepbound and it's stunning how my favorite beer...the one I craved and tasted so good 'why don't I have another?'...no longer has a hold on me. I could take two or three sips, set it down, and walk away. I also now feel full, but not disgustingly over-stuffed now.
- guerrilla 1y ago
  You can't outrun a bad diet. You can easily out-eat any exercise though. Check just how few calories stationary cycling for an hour burns. I can eat that many calories in 5 minutes.

Nesco 1y ago

I am pretty sure uncouplers will make a come back. Just something a little more targeted and safer than good ol’ DNP

nkmnz 1y ago
looking for this, hu? https://en.wikipedia.org/wiki/HU6 https://en.wikipedia.org/wiki/HU6
- Nesco 1y ago
  Yes, but also BAM15 and mRNA based UCPs overexpression Longer term if it works more research in the domain, including variations of the other well known ones (DNP, XCT-790, mitoCCCP, …) I firmly believe that combined with: - additional progress on the current targets (GLP-1, GIP, …) - compounds to counteracts muscle loss like myostatin inhibitors - food options being shaped by more health conscious consumers Having a slow metabolism will stop being an disadvantage by midcentury
loeg 1y ago
But why? Ozempic et al solve the input end of the equation. Burning more and literally being warmer isn't better.
- cthalupa 1y ago
  I would agree, personally - I won't go near DNP, and even the newer stuff like BAM15 that is supposed to be incredibly selective I am quite suspicious of. But you still see people losing tons of weight on GLP-1s wanting it to go faster, drop more pounds, etc. I'm a big proponent of them - and I have enough risk tolerance that I'm on grey market retatrutide - but I see a lot of people that want to just keep adding more and more chemicals to the equation to solve the issue. I've taken the time to significantly modify my food and exercise habits, and believe that I'll be able to maintain my weight loss if I were to go off of the GLP-1. But a lot of people haven't. They eat the same bad food, just in lower quantities, don't increase their protein and fiber intake, don't exercise, and just up the dose or add a new compound when their rate of weight loss doesn't satisfy them. There's tons of interest in BAM15, clenbuterol, and all sorts of experimental substances. Tons of people taking things like tesamorelin and ipamorelin too. I think the GLP-1s are basically miracle drugs that have allowed a lot of people, including myself, to totally revamp their approaches to diet and fitness. But there's a lot of people that are going to be more than happy to increase their cocktail with anything they think will get them skinny faster.

jxf 1y ago

> If Ozempic is so great then how come our bodies don't just produce more GLP-1? We don't know. But one early signal is that you lose an atypical combination of muscle mass and not just fat, which is not a good evolutionary adaptation if you are an endurance hunter. https://healthcare.utah.edu/newsroom/news/2025/08/new-study-raises-questions-about-how-ozempic-affects-muscle-size-and-strength https://healthcare.utah.edu/newsroom/news/2025/08/new-study-...

Nursie 1y ago
Muscle-mass loss is normal on any weight-losing diet, and the link says it is actually less than expected…

eru 1y ago

> The second point I haven't seen discussed is that weight loss drugs prior to GLP-1 agonists include cigarettes, which (worst case) give you cancer; [...] Nicotine works just fine as an appetite suppressant without the carcinogenic tar you get from burning tobacco leaves. Similar for other stimulants or stimulant-like substances. But I agree that they get a bad reputation, despite actually working pretty well, and with manageable side-effects: not worse than what I've heard about the nausea people get on GLP-1 drugs, and much better than the health effects of obesity.

loeg 1y ago
YMMV but personally I did not find nicotine an effective appetite suppressant.
Telemakhos 1y ago
Nicotine, even without the tar, reduces your nitric oxide levels leading to vasoconstriction, damages endothelial health, and can lead to atherosclerosis. You're much better off eating less and making more time to exercise instead of ingesting foreign substances to compensate for bad habits.
- eru 1y ago
  Compare and contrast https://gwern.net/nicotine https://gwern.net/nicotine

benchly 1y ago

> If Ozempic is so great, how come our bodies don't just... While I agree with your sentiment, your argument here assumes the human body always makes intelligent decisions for itself. My obstructive sleep apnea would like a word. After it's done choking me awake, of course. The body is a marvelous machine, but it is far from a perfect or intelligent design. We are lucky to have what we have, but expect operating mistakes.

wisty 1y ago
Evolution should make intelligent choices for us but there's thousands years where a few extra pounds meant surviving a famine. Also I bet it will kill a few people with eating disorders. As long as you're in a 1st world country and have a BMI over ... maybe 25 (and aren't on steroids so you're both anorexic and overweight at the same time) I'd guess you're dodging a lot of the most obvious risks.
- benchly 1y ago
  How do you define 'intelligent' and 'evolution?' I think we might differ on what those words mean, which would make this conversation difficult, so let's clarify where each of us is coming from. My understanding (which may be slightly misguided because this is definitely not my field) is that Intelligence is the ability to use information for reasoning, decision making and achieving understanding. This ability, as a directed action, only applies to creatures with consciousness. Regarding evolution, my understanding is closer to a process that is more akin to a passive filter, with no guidance to speak of unless we want to stretch the limits of the concept of guidance to encompass survival, which is the genetic materials of those who survive the environment getting passed on, which would also implies that sometimes garbage/noise stays in the gene pool. While information (genetic material) is being passed on, it is not being selected through reasoning or consideration, but more of a mechanical process (although there's an argument to be had that we, humans, might be changing that game). How would you define those words? Happy to consider understanding different than my own, since I do find it interesting.
  - wisty 1y ago

highfrequency 1y ago

"No free lunch" is not good intuition for many biological processes. There has been near zero evolutionary pressure toward improvements that primarily manifest after age 60. Separately, evolution took place in a very energy and calorie constrained environment which is very dissimilar to today's world. Many people do not feel spontaneous desire to fast or run laps even though these are clearly beneficial.

Fargren 1y ago

> if it would improve the evolutionary fitness of the majority of people Evolution led to the intelligence that led to creating Ozempic. Maybe that's the mechanism by which evolution is improving evolutionary fitness. The idea that what was created by man is not part of evolution is part of the naturalism fallacy; it's the false belief that the domain of nature stops at the doors of the lab.

fnord77 1y ago

"no free lunch" usually boils down to violating some law of thermodynamics. since we're preventing the body from adding excess potential energy to the system, I don't think this is violating any no-free-lunch rules.

AngryData 1y ago

I agree with you overall, but humans atrophying muscle away so rapidly, and also building muscle so quickly, is fairly unique to humans so im not sure there has to be a downside to being shredded all the time like a gorilla through some sort of medical treatment in the future. We certainly haven't figured that out now, but I wouldn't be surprised if some gene therapy and chemical cocktail couldn't allow it safely someday. From everything ive seen it seems to be just a calorie saving adaptation so more energy can go to the brain. And perhaps make more varied and specialized living strategies, made possible thanks to our brain, more efficient by not supporting large muscle groups we don't always need. Of course maybe its not possible, but it is the default for pretty much every other animal so its not like it is trying something completely outrageous like trying to eliminate sleep.

lo_zamoyski 1y ago

> cheese grater abs Washboard abs?

jart 1y ago

It only makes sense if you understand that everyone is being poisoned, and this is the cure.

VeejayRampay 1y ago

that's not why we get fat we get fat because of the american diet, priori to which people in the world were actually not that fat the lack of fermented food, the epidemics of ultra-processed, ultra-rich and grotesquely fat and sugary food is why people have gotten fat, which is a relatively recent phenomenon (and which is not as widespread in culture that resist the American diet the most like the French and the Japanese)

wkat4242 1y ago

> If Ozempic is so great then how come our bodies don't just produce more GLP-1? Because our bodies have been tuned to deal with food shortages for hundreds of thousands of years. Now we live in an age of abundance but our bodies still try to harvest each calorie they can get. If this continues we might evolve to no longer store surplus calories as fat. Though I doubt it because the age people die from overweight related issues is way after the age most people have kids at. But I imagine that soon we will be able to directly tune some of that evolutionary bagage that no longer applies, by gene modification.

gniv 1y ago

This blog post by Derek Thompson answered a lot of questions for me: https://www.derekthompson.org/p/why-does-it-seem-like-glp-1-drugs https://www.derekthompson.org/p/why-does-it-seem-like-glp-1-... In particular it seems Ozempic has anti-inflamatory effects which could explain a lot of these non-weight-loss-related results.

tomrod 1y ago

> our bodies don't just produce more GLP-1 Dominant subgroups in a species are dominant because their parents survived that last set of pressures (external death inducements) at a higher rate than other subgroups -- but won't necessarily see the same results with the current set. Even 90 years ago, there was significant loss of life due to famine, so selection was towards people who could efficiently gain and store calories in a biological Keynesian strategy. Now we have the opposite problem -- abundance of life-sustaining food produced for cheap but good quality food is expensive (in the US -- many other parts of the world have their quality food cheaper but I digress). So there hasn't been enough pressure (external-induced death) for GLP-1. As a species with a remarkable ability to modify its environment to suit our purposes, body response to disease is just another thing to modify.

FeloniousHam 1y ago
> but good quality food is expensive (in the US -- many other parts of the world have their quality food cheaper but I digress Let's digress. I read this frequently in various forms on this forum, and it's always "just so" justification. My own heuristic thought is that "low quality" food (high energy, long shelf-life processed foods) is very cheap because it is produced at scale and can be stored, while "high quality" (fresh products) is not cheap for the opposite reason. The US has the cheapest food in the world [1]. Expensive food is expensive, but I would bet quality food is cheaper here than anywhere else. The "problem" is that when presented with a cheap, easy, tasty, high calorie food option against a relatively more expensive "quality" option, consumers choose the former because it's cheaper, easier, tastier, and provides more calories. I would bet this is even true when the absolute difference in price is small. [1] https://www.fastcompany.com/91208387/food-grocery-prices-us-world-comparison https://www.fastcompany.com/91208387/food-grocery-prices-us-...
- tomrod 1y ago
  > Expensive food is expensive, but I would bet quality food is cheaper here than anywhere else. Having lived in a few other countries with less industrialized distribution networks, no, this claim is dramatically incorrect. Fruits, vegetables, staples like rice, and basic forms of protein (fish, insects and sea critters, some chicken) are much, much cheaper relative to processed foods. Larger protein sources like beef, pork, or bushmeat is relatively more expensive, however, unless you opt for poor quality processing like cheap "corned beef" made from offal. As an economist, I appreciate the difficulty of making apples-to-apples comparisons across countries for things like food prices, as even the acclaimed "Big Mac Index" assumes that a Big Mac has a similar relative status across countries (though the oft-misunderstood intent of the Big Mac Index is to more to compare consistent production costs). In some places a Big Mac is fancy, in the US it is considered fairly garbage but consistent. For example, in a market in the Philippines, you have mostly cash transactions and informal capture for what the majority of people purchase. The purchasing is done more in these almost farmers-market style transfer versus grocery stores in the US. They _do_ have grocery stories, but almost uniformly for processed food distribution versus fresh food in the markets. It's much cheaper to eat healthier from the markets and through the informal distribution network of sari-sari stores versus equivalent nutrition from processed food from the grocery stores. Also, consider the results of this recent study: https://arstechnica.com/health/2025/08/in-trial-people-lost-twice-as-much-weight-by-ditching-ultraprocessed-food/ https://arstechnica.com/health/2025/08/in-trial-people-lost-...

physPop 1y ago

Because over the course of a billion years of history, evolutionary pressures essentially end after child-rearing ages.

jghn 1y ago

> if it would improve the evolutionary fitness of the majority of people The issue with this logic is that evolution tends to find local, not global, maxima

sumeno 1y ago

If not having cancer is so great why don't our bodies just not make cancer cells? Weight loss aids are given far more scrutiny because people wrongly view it as a moral failing

ifyoubuildit 1y ago
As I understand it, species that are really good at healing from injuries are more likely to develop cancer. So evolution has to optimize for survival via healing vs survival via not getting cancer. Some people probably do come at it from the moral angle. But there are good reasons to assume that this time isn't different, that there is indeed no free lunch. Thankfully, everyone is free to make that risk assessment themselves. Just don't start trying to force it on anyone.
- sumeno 1y ago
  It seems like you really missed the point. Of course there are reasons we still get cancer, just like there are reasons people get fat. Evolutionarily people are way more likely to die of being under nourished than over, so the body packs on fat when it can. Evolution did not optimize for 2025 > Some people probably do come at it from the moral angle. But there are good reasons to assume that this time isn't different, that there is indeed no free lunch. I'm struggling to understand what these sentences even mean. A medication may have side effects? Like every single medication we take? Yeah, of course it might. We don't have threads clutching their pearls about most medicines though. Tylenol can easily kill you if abused, but we don't have threads talking about how there's "no free lunch" for people using Tylenol responsibly. > Thankfully, everyone is free to make that risk assessment themselves. Just don't start trying to force it on anyone. Who is saying anything about forcing something on you? Is someone trying to force you to take Ozempic?
  - ifyoubuildit 1y ago
    > It seems like you really missed the point Yeah, I guess I don't really know what your point was if it wasn't to ask why we get cancer. Maybe that's my fault? > A medication may have side effects ... beyond the initially understood ones. Tylenol has been around for a long time. When it first came out, people were probably popping it like candy until they realized the limits, and now it's pretty well understood. And who cares if people are "clutching their pearls"? What harm does that do? > Is someone trying to force you to take Ozempic? Not yet, but I won't be surprised if people start pushing for it. Think about things like soda laws and seatbelt laws. If my being obese is costing you tax or insurance dollars and we have this magic pill, it's only a matter of time before the machine does its thing.

api 1y ago

Natural selection optimizes for long term survival of genes. Humans are probably long-lived because we have high maintenance offspring and a survival strategy built around communicating culture, but this only necessitates survival through 2-3 generations worth of time. Anything beyond that won't be selected for. Same with health, etc. A bio professor once said "life doesn't work perfectly, it just works." There's a lot left on the table because evolution optimizes for the median case over time.

paulcole 1y ago

If insulin is so great why does my pancreas simply not produce it?

JumpCrisscross 1y ago

> If Ozempic is so great then how come our bodies don't just produce more GLP-1? Idk, why can’t we synthesise vitamin C? Why do we have a bent oesophagus prone to choking and heads bigger than womena’ hips? We weren’t intelligently designed. To the degree we were optimised for anything it isn’t the modern environment. A lot of pushback against medicine in general seems to derive from an underlying belief in an innate perfection of human biology.

fc417fc802 1y ago
Both of your examples have no straightforward solution. Whereas we already have the mechanism in question so the question "why doesn't it just ramp up" is quite reasonable. Biology is a highly tuned system.
- JumpCrisscross 1y ago
  > your examples have no straightforward solution In humans? No. In our ancestors and every other animal around us? Yes. > we already have the mechanism in question so the question "why doesn't it just ramp up" is quite reasonable Our species almost got wiped out in an ice age less than a hundred thousand years ago [1]. It's possible we had the ability to ramp up GLP-1, but that it got eliminated in a famine. [1] https://www.npr.org/sections/krulwich/2012/10/22/163397584/how-human-beings-almost-vanished-from-earth-in-70-000-b-c https://www.npr.org/sections/krulwich/2012/10/22/163397584/h...
  - fc417fc802 1y ago
    > In our ancestors and every other animal around us? Yes. Right so my point is, with no smooth optimization path towards X in a given species the question "why doesn't species just X" has a readily available answer - because biased random walks are fickle and the pathway likely convoluted. Whereas when a smooth optimization path is available it becomes reasonable to ask "then why isn't species doing X already"? Assuming a long enough timescale then there must be some selection pressure preventing it. I agree that the ice age is a reasonable hypothesis. If we were exposed to repeated boom-bust cycles of extended duration (ie multi-generational) then it's at least plausible that we gained some mechanism dedicated to preventing us from adapting in that direction. Still it's an entirely reasonable question that needs to be asked when considering the potential for serious side effects. If the hypothesis is that this is actively prevented for historical reasons then we should want to see the precise molecular mechanism hunted down in order to validate that. Keep in mind that an alternative hypothesis would take the general form that ramping it up causes serious deleterious side effects in the long term. It's quite like Chesterton's fence. There must be a reason so we would do well to understand approximately what that might be before tinkering.

random3 1y ago

I'm one of those watching on the side, wishing there would be a holistic, aggregated, view on all pros/cons that highlight each results statistical relevance as well (in particular it'd be great to understand test samples). On the natural evolution. I think it's best to think of it as a proces, with optimal state being a limit (e.g. in time, in total population), but especially in a changing environment. So, as it became easier to procure/produce fats or sugars there can be local sub-optimal states. So, in this framework, th "how come our bodies don't just produce more GLP-1?" question, can be answered with the fact that it's possible that we just haven't adapted yet. If we end up back to previous availability.— e.g. we lose farm land and "starve" again it would end up being the right evolutionary speed, if not, those that naturally produce more, may end up becomign majoritary. The bottom line is that natural evolution is a long term process that's adapting things to long term changes and "long" here can mean many generations. In a sense, philsophically, I wonder what prevents our own "changes" to be just a natural evolution of the natural evolution— i.e. a "conscious" evolution.

dbliss 1y ago
I always wondered if evolution through natural selection has essentially halted for humans for the most part. My thinking is even the previously most likely to die before child bearing has been reversed by modern society. Given that it happens at such a long time scale and modern humans and technology hasn't be around that long in the grand scheme of things it's probably not true, but I always found it interesting...

CyanLite2 1y ago

Our bodies haven’t evolved yet to produce more GLP-1 because until recently (~70 years ago) malnutrition and hunger had been one of the top killers of humans. Frankly put, we weren’t designed to live this long. We’re designed to consume calories and store those calories indefinitely to meet short term needs, rather than lifelong health. But we weren’t also designed to consume microplastics, artificial sweeteners, or flavors designed in a laboratory. Yet here we are. And it’s quite probable those things contribute to obesity.

42772827 1y ago

> If Ozempic is so great then how come our bodies don't just produce more GLP-1? How come we aren't like chimps, with eternally shredded bodies and cheese grater abs, provided we get the protein to support them? Evolution favored this level of GLP1, then we invented agriculture, and cooking, and bliss points. Now it’s far easier to ingest massive numbers of calories in ways that our old world systems can’t properly signal against. Evolution hasn’t caught up and maybe never will.

loeg 1y ago

> "No free lunch" is a reasonable question to ask when evaluating medication, if it would improve the evolutionary fitness of the majority of people. I think this is behind some of the skepticism. If Ozempic is so great then how come our bodies don't just produce more GLP-1? We can do science and technology on timescales vastly faster than evolution. "Why didn't evolution do it?" is just a very irrelevant question. > The second point I haven't seen discussed is that weight loss drugs prior to GLP-1 agonists include cigarettes, which (worst case) give you cancer; stimulants, which cause your heart to fail; parasitic intestinal worms, which can kill you but more importantly are just plain gross; and mitochondrial uncouplers, which set you on fire at a cellular level. That's a long history of miracle weight loss drugs which turn out to have horrible side effects. Cigarettes, parasitic worms, and 2,4-DNP were never medications.

spauldo 1y ago
Tobacco, and cigarettes in particular, has been used as a medicine for hundreds of years. And it's not just in the distant past - a friend of mine was actually prescribed cigarettes for anxiety about 30 years ago here in the US when he was 14. There are various health benefits to smoking, believe it or not. They're just outweighed by the downsides.

elzbardico 1y ago

"No free lunch" is a heuristic, a useful one most of the time, just that. But it is not a hard nature law such as the speed of light in vacuum.