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.
DNP and stimulants I'm more confident of, nicotine and tape worms I'm a bit iffy about.
It's definitely a stimulant in colloquial English, just not in pharmacology.
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.
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.
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.
Time to burn that Gym membership :-p
(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.
Heat retention would benefit an ambush hunter in a cold climate whereas heat exhaustion is one of the ways endurance hunters catch their prey in hot climes.
> Humans are also hairless endurance hunters
It's something we can do but the diversity of habitats, prey and techniques humans feed themselves with is far greater than what feels like an over-indexing on specific extant savannah tribes as if they are proto-human relics. Do you need to out run a fish or an oyster? Why would you run after a rabbit instead of waiting for it near it's burrow? etc.
Personally I bear little resemblance to an endurance runner so one might assume no shortage of forest/mountain dwellers in my genes given short thick legs. Built for sprinting, climbing and carrying but, to my despair, incurably injury prone at endurance running.
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.
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)
Source: have to do keto diet and be strict to stop food addiction.
Why would you ask old people if young people are healthier than they were? Surely, Spain compiles medical statistics.
Anyway, Spain appears to have the same weight issues as everywhere else:
Those numbers are relying on how long the older generation lives. If the younger people are physically more active, how do you know that they will also live as long? It could be that modern expectations of what a "healthy" body should look like takes it too far, and that you will end up with a shorter life.
I see a lot of former athletes dying in their 60s/70s from heart failures and other conditions. Perhaps the body has limits to how much abuse it can take.
People who don't experience difficulties moderating their diet and could flounder their "self discipline" are now on a level field with people who did have difficulties with their diet. So they feel threatened by it.
Another example of a world in which people are not challenged to grow as people; instead of being happy that more people can get healthy they dismiss the medical advances as "moral failures" since they can no longer feel superior.
I'm continually frustrated with the four thousand year old history of people being surprised that other people "don't just ${something good for you} and don't just stop ${something bad for you}." Great, we've tried the "Acting surprised people do unhealthy or bad things" strategy and the "scolding people for doing unhealthy things" strategy for a couple millennia and people still do the things.
Will we continue this strategy or will we try something else now?
Why were there no obese (poor) people 100 years ago?
what i mean is, on one side you have huge teams of absolutely brilliant well-resourced food scientists A/B testing their products to maximize addictiveness and other related metrics. On the other side you have a stressed out parent tired from a full day of work just trying to quickly get some food for their family.
This isn't fair! It should make you angry when you see regular people who are probably a lot more like you than you think being preyed on by others
But I think these drugs are awesome. I have family members who are obese and don't seem to have whatever I have that allowed me to lose weight the old-fashioned way. I hope they'll be able to lose weight safety with the drugs.
Sometimes people just need a helping hand. There is no shame in that.
It appears your issue is that you just don't think its fair and that people should have to take the long way. I would argue that's a you issue and not an us one.
Our bodies are just too efficient. We can't "outrun the fork" (unless it's our full-time job). We must modify our diet. Which is not easy for many reasons.
At some point I think you just have to accept that the whole point of socialized medicine is to just make sure people get healthcare regardless. If you want to engage in some kind of market analysis and means testing, you can always live in America, where it's guaranteed that people get exactly as much healthcare as they deserve, since net worth and liquid cash is correlated perfectly with an individual's moral success.
I'm pretty sure there are benefits far beyond looking better.
I see many who were overweight lose weight and get ripped, while others have no chance to reach that far. Someone with a BMI of 40 has basically ruined their body and while they may look better with a shirt, they will keep it on while on the beach because of the excessive skin.
The reward and motivation for a person with a few pounds extra and a truly obese person are simply too different. Someone who has not reached whatever weight threshold that fits their body type has a chance to look "normal", while the more obese person will reach a point where losing more weight has less impact even after plastic surgery.
Take Elon Musk, he is clearly overweight. Is your argument that he lacks self-discipline as a person and is as such a complete failure? Of course not, the man is clearly more disciplined and driven than most people. He just eats like crap as he has other priorities.
I am open to you explaining the argument as to why 40% of people being obese so that they have to learn self discipline in just that single area of their life and all of the associated social, health and financial costs is more beneficial to society as a whole than people taking a shot and losing weight and gaining all of the benefits that being obese robs society of.
Society evolves as its technology does. I'm sure its not the case but your argument appears to devolve to "Back in my day we didn't need a shot to be thin like you young kids, we walked up hill both ways to school with our little brother on our back. IN THE SNOW!"
Driven by huge amounts of ketamine and a pathological need to reproduce, perhaps.
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
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.
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)
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.
The interesting thing is that once I switched to a keto diet, my body mass changed and my health improved significantly for the better. The interesting thing is that the keto diet is actually higher calorie than the high carbohydrate one.
I suspect that telling people they need to exercise more is not helpful - most people will never be able to exercise at a level that will make a dent in their diet. A lot of people are eating 4,000+ calories a day of high carbohydrate diet burning 50-200 calories per hour. The math just doesn't work. The diet is where it is at.
Plenty of ways around it. Some people have a treadmill or spin bike desk setup. Powerlifting doesn’t take much time. You can also eat less.
Our lifespans have increased with our sedentary lifestyles.
Exercise is part of it. But we’re clearly working to transcend our natural health spans in a comfortable, modern environment. That will require the application of intelligence to the problem, not just brute force.
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
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.
The issue with regaining weight after coming off these drugs is that people don't change their habits, and once they are off, they no longer have the limited appetite, and return to eating like they did before, which just results in the problem reoccurring. Uncouplers won't change this.
If people want to sustain their weight loss, they either need to change their lifestyle and eating habits, or they need to stay on the drugs, and potentially even both.
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-...
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.
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.
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.
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.
I was being cheeky, not using the best word for the job.
Evolution is not really passive, it's a combination of mutation (which is not intelligent, but not really passive) PLUS a passive filter, which gives the illusion of intelligence since it ends up as a kind of optimiser.
Now, due to various factors, evolution isn't perfect. For gene expression reasons (I think) the layout of mammal skeletons are not really effected much mutations, but bone sizes are; so you have giraffes with huge neck bones that are the same size as human neck bones (this isn't the best way to do it). You have bats with the same finger bones as humans (or at least very similar) acting as wings. Elephant feet are almost the same as human feet in an x-ray. Some genetic "knobs" are easier to turn than others, and it can be that shrinking something is easier than getting rid of it. Just google "vestigial structure". Actually, LLM are kind of similar (it's easier to optimise a value to zero than to remove it, even if removing a value will make the model better and faster).
It's also more adaptative than optimal. Some argue it's the "selfish gene" that "wants" to be passed on. If a gene makes you kill all the competition, that's a "fit" gene. If working in a team increases the survival rate of your cousins (who also kind of carry your genes) it's "fit". If having a certain percent of a village be gay would somehow increase survival rates (especially of their kin) then having a chance of being gay is "fit" even if the individuals themselves could be less likely to reproduce.
There's also some meta stuff about how the rate of mutations could partly be genetic.
Evolution is seen as intelligence because it solves hard problems, and IMO that's kind of the only thing intelligence needs? People who talk about "consciousness" talk a lot about how they think they think, but is how we think actually an illusion? The feeling of understanding is just a chemical pleasure hit when the brain hits the "problem solved" button. Consciousness might be an illusion, we might make a decision and wonder how we made it, then an AI in our brain quickly justifies it in some BS way that isn't actually our real thinking process.
And I think that we can only expect the process of evolution through natural selection to operate on traits that cause differential survival of individuals before reproduction. All sorts of new traits acquired through random mutation and recombination that only affect individuals after typical reproductive years will exist even while natural selection is still operating. The answer to “why doesn’t the human body operate like [some idealized state]?” Is either 1) insufficient time has elapsed to allow natural selection to change the gene pool, or 2) It doesn’t affect survival before or during reproductive years. (Or, I suppose a third explanation is that the required mutation that drives the change just hasn’t happened yet. Our species hasn’t been around that long after all!)
If in a hunter-gatherer society most people stop reproducing after 40 (not entirely realistic, but bear with me), me being alive and fit at 45 can still improve the survival of my genepool. I can hunt meat and gather plants to make sure my children and grand-children are well-fed and able to produce plenty of offspring, carrying my genes on. I can build shelter, care for the young (improving their survival chances and freeing up the parents to do more physically demanding work).
And my siblings share half of my genes, and my cousins a quarter (assuming no inbreeding at all, otherwise the numbers go up). So helping their children survive and proliferate is a win for the proliferation of my genes. Evolution gets less effective the more indirect the effect and the lower the gene contribution, but it doesn't completely stop working. If there is one clan where everyone dies at 30 and one where people stop reproducing at 30 but stay useful members of society until 60 then then the second clan will do better and outcompete the first
We know that there is strong selection pressure for things that occur during reproductive years. No one debates this.
How much the sort of scenarios you're discussing impact selection pressure is significantly less clear.
But it's also a moot point for this discussion - we haven't been in a world where people can get this fat so easily and in such large quantities for long enough to make significant impact to evolution even if we assumed that selection pressure works the same in said world - and again, we know it doesn't.
But even if there is it doesn't mean that there is any reason whatsoever that increased GLP-1 production would be enough of an advantage to have had significant impact on evolution. We're going from A is true, B is likely true, C might maybe be true, all the way to Z is definitely true.
After industrialized nations have reduced both maternal mortality and violent death (warfare) to small fractions of their pre-modern levels. The life tables of 1500, 500, or 5000 BC would look very different than their modern versions.
I don't think the argument holds so strongly for questions like "why don't we produce GLP-1 hormone at a 20% higher level?" Increasing GLP-1 production levels seem like a smoother transition with fewer side effects. If higher production is better, and you've got an SNP that increases production by 5% on its own by increasing the number of L cells in your intestines (or something), that sounds like it should make you more reproductively viable in today's world and shouldn't have as high an impact on everything else as changing the shape of a throat.
Most of this is just my intuition, and I'm absolutely not an expert.
Edit: final note that I think in today's world is the key gotcha here, per the original text: "getting fat in times of plenty was a feature and not a bug", meaning that it was evolutionary advantageous for most people to put on weight until very recently, evolutionarily speaking.
And it will perpetually remain possible for it to very abruptly and unexpectedly prove advantageous once again.
Primates in the wild really hit the nail on the head here. We clearly lost the equivalent at some point and haven't rapidly regained it. There has to be a reason for that (though it might well prove to be entirely incidental).
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.
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.
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.
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.
Washboard abs?
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)
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.
In particular it seems Ozempic has anti-inflamatory effects which could explain a lot of these non-weight-loss-related results.
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.
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-...
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-...
Neither one of us pursued this.
Matches my experience. I too would contest that reasonable quality food is more expensive. In my experience it's actually somewhat cheaper by any metric except $/calorie and even then you could just add butter or oil to the "healthy" alternative to juice the numbers.
I think the primary differentiator is convenience. Grabbing an actually rather expensive box from the cupboard beats out spending 30 minutes cooking and another 10 cleaning.
The issue with this logic is that evolution tends to find local, not global, maxima
Weight loss aids are given far more scrutiny because people wrongly view it as a moral failing
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.
> 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?
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.
Some people think things will be great, and we've already got everything figured out. Other people are not so optimistic. Neither side knows the future. There is no "truth" here that you have exclusive access to.
This is why I said it's great that everyone can make that risk analysis themselves. If someone comes along and takes these meds off the market for no good reason, then there's something to complain about.
> Is someone trying to force you to take Ozempic?
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.
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.
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/h...
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.
I agree about it being asked. A lot of times it isn’t being asked, but assumed.
I thought it was snake oil when announced. I’m now beginning to question if it’s closer to a weird vitamin that we face a systemic deficit of.
There's some studies suggesting that a big part of what influences someone to naturally be fat or skinny is tied to natural production of the GLP-1 hormone. Post-prandial readings of serum level GLP-1 show significant differences in lean people vs. obese people, with obese people have much less.
We don't have an understood mechanism yet to determine if it's causative - maybe it's yet another feedback loop we have with gaining weight - but it seems very plausible that the natural level of production is a determinant factor in just how susceptible you are to packing on the pounds in today's food-rich world.
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.
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.
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.
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.
There are various health benefits to smoking, believe it or not. They're just outweighed by the downsides.
But it is not a hard nature law such as the speed of light in vacuum.
And then I saw some of the stories on HN about how it's changed peoples lives for the better. And then people in my life started taking it and singing its praises. I'm very bullish on GLP-1s now and I've very excited to see all the lives it improves. I'm not saying this thing is 100% miracle with no downsides, but this seems to be a generally large net positive.
It's a bit hard for me to comprehend how big of an impact this can have for someone since I've been very fortunate to never struggle with my weight, but I'm (slightly embarrassingly) tearing up writing this because of how many people I've seen have huge positive effects on their physical and mental health (due to body image).
Like, I figured we were just never going to solve it, given the two possibilities were "radically re-engineer US culture such that moving to the US doesn't make previously-skinny people fatter" (with other countries heading the same direction as us needing to make similar moves, one supposes) or "find a miracle drug". Neither seemed likely. Turns out, decent odds we've managed the latter! Which was always the more likely of the two, but I still wouldn't have rated it as very likely.
What matters is, are the negative side effects and long term consequences better for you than the alternatives. One of them is "remaining fat". The other is "doing what other people have proven works.. cut all carbs".
Is ozempic worse than being fat?
Individually, there's (previously) been nothing better to suggest than "try harder (and, maybe, smarter)".
Statistically it was almost useless, but it's the best we had. It's not bad advice exactly, it's just extremely unlikely to work for long-term, sustained weight loss.
It also very much appears to be the case that weight gain and loss are heavily influenced by environmental factors. Skinnier countries aren't skinnier because the people there have more willpower, it seems, but because they live in a skinnier country and are surrounded by the culture, laws, physical layouts of the created world, et c., that come with that. It'd be kinda weird if we expected "just try harder" to work very well when that's evidently not the mechanism by which skinny countries are skinny. Alternatively, if it is willpower doing it, we're just adding a step, because then it appears that environment strongly influences willpower, instead, since the same observations hold.
Sure, sometimes it works for individuals. In fact, it often works temporarily, causing a yo-yo effect. It can work for long periods (many years without a slip) but that's rare.
If your solution to the obesity crisis is "people need to try harder" your solution is demonstrably not helpful. Can it work for one person? Yes. Over a population, will it? No, it won't, it's amazingly ineffective, even very expensive high-touch interventions involving multiple experts aimed at weight loss and lifestyle change and such are wildly less effective than "inject GLP-1 agonists" or "move somewhere skinnier".
> In the 1970s, Jens Juul Holst and Joel Habener began research on the GLP-1 hormone [...] Research continued, and in 1993, Michael Nauck managed to infuse GLP-1 into people with type 2 diabetes, stimulating insulin while inhibiting glucagon and bringing blood glucose to normal levels. However, treating diabetes patients with GLP-1 hormones resulted in significant side effects, leading researchers financed by Novo Nordisk to start looking to develop a suitable compound for therapeutic use. In 1998, a team of researchers at Novo Nordisk led by the scientist Lotte Bjerre Knudsen developed liraglutide, a glucagon-like peptide-1 receptor agonist that could be used to treat diabetes.
GLP-1 is a hormone that naturally occurs in the human body. Novo Nordisk was responsible for turning it into a diabetes medication. They were responsible for turning it into a weight loss medication.
Where are you getting your facts from?
Other "newcomers" in the GLP-1 space are also showing more promise than what Novo has in the pipeline. Boehringer Ingelheim has Survodutide in the pipeline as well, along with plenty of others.
They're the least interesting game in town when it comes to the incretin mimetics at this point.
> If your solution to the obesity crisis is "people need to try harder" your solution is demonstrably not helpful. Can it work for one person? Yes. Over a population, will it? No
Are you an individual or a population though? Take off the telescopes (and data, and science), and look at the world through your own eyes.
No one needs (or can) to address the obesity crisis in the population. The only crises that can be solved are the ones individuals find in themselves.
Lots of people successfully make changes and lose weight, but exceedingly few manage to keep it low over time.
My assertion is that the success of long term weight changes is not independent from that variable.
There's no evidence to suggest that reading comprehension or scientific aptitude has any link whatsoever to ability to maintain the willpower to stick to a diet. It seems distinctly non-obvious to think it would matter.
And all the evidence is that diets works soo poorly that the effect would need to be astronomical for it to counter-act just how unlikely they are to effect lasting change.
People in the US eat absolute shit. Even the bread is full with sugar.
Good for capitalism if you can feed that to the people and then give them an injection to be healthy again I guess.
Do we have data on that?
I guess you could look at natural experiments, like people who lost and won H1B lotteries, and see if only the ones actually making it to the US get fat?
My dad has finally understood that grains are for people that need help maintain weight or gaining weight.
No fat person should ever be eating them.
It's strange to make the culprit of a modern epidemic foods that have been with us for millenia.
I said in my other posts.. if someone needs help maintaining or gaining weight, eat those things.
If you are overweight, you should be eating ZERO of them.
"Basically killing them" means whatever the current obesity and type 2 diabetes epidemic means.
I know it's hard to believe in the US as today it even gets harder in Germany to find it.
The problem is eating shitty cheap mass produced food.
Same goes for "vegetable oil". Check out how it is made and you will probably respect olive oil more or some good ol butter.
Also it is possible to drink water. You don't need soda from dawn till dusk .
> No fat person should ever be eating them.
This is absolutism and controlling. Carbs have their place in a balanced diet, but key emphasis on diet. Too much (like the US diet) isn't good, none at all isn't good either. Everything in moderation. I don't understand why dieting / weight loss conversations are always going into extremes and absolutes.
What’s weird about it? Is insulin some weird injection? What about epinephrine?
It seems like a lot of people need something other than "don't eat bread" though.
And he is extremely happy with his new sugar and bread free life of increased mobility, less pain, and much lower blood pressure. At 64, he's learning how to ride a dirtbike and doing pretty well at it.
You're clearly an advocate for your father making healthy choices. So why would you advocate against the use of a drug that makes that easier?
Unless we talk about eating disorders.
Telling your mind to do a thing is only ever easy in retrospect and when you find a "trick" that works for you. For some people that trick is getting clear feedback about glucose levels in your bloodstream. But any trick that works for one person might not work for the next. So it is good that there are many approaches.
People make such a moral crusade of this - the drug works, people will take it. Behavior modification works in theory and fails for most in practice. Even for those that can make it work usually don’t hold out indefinitely.
We likely agree that doing it without drugs is probably better, but it’s definitely harder and it’s not clear yet how much better it will even be.
I’ve successfully lost 70lbs (250->180) three times and gotten fit, but it’s a constant effort and psychic drain to maintain the lower weight. If the drug (which I haven’t taken yet) made it easy that’d be a relief. It’s much easier to just manage exercise.
I suspect people that don’t have as much difficulty just get a different amount of joy from eating. For me I felt I could relate to the way an alcoholic described trying to quit drinking, except it’s harder in a way because you have to eat.
If changing your habits was much easier then we wouldn't need these medications and the world wouldn't keep getting fatter. People have known how to not be fat for a long time, yet the obesity rate has been rising worldwide, even in countries that have traditionally been skinny.
It's not like fat people on the whole are ignorant of how to become not-fat and never attempt to do so.
And it’s exactly the same situation with financial education, debt, university degrees, or in general any long term endeavors that requires the sacrifice of the immediate pleasure.
Of course, we still have a non trivial percentage of people that suffer from eating disorders, and use food as a way to emotionally regulate themselves because that’s what they learned as children (child is unhappy, give him a candy…).
I don't understand what drives people to write such intentionally asinine comments. Do you get off on hurting others or something?
There were quite a few foods I let go of when I decided to drop weight. Can't say I miss them much, certainly not to the extent to say something like "wow, i can't enjoy food anymore" or "now i'm fighting cravings all the time!!". And I legitimately have no interest in reintegrating them into my diet.
Turns out, some kinds of food are just dumb to consume, and my enjoyment of them is legitimately secondary. To the extent that discovering how harmful they were, they became inherently less enjoyable, and it was well possible for the habits and the cravings to subside over time. You don't try to go hit a balance with crack addiction, why would you try to hit a balance consuming 5 bazillion calorie rubbish?
Cutting out certain classes of foods from one's diet is absolutely possible and there's nothing necessarily wrong with it.
Your story has been told over and over and over. We get it. Congratulations. You win. You don't need GLP1s to sustain your weight loss. You don't experience food noise. You made all the right choices. Your brain and genetics are superior to the 30% of American adults who have been told to eat less and move more and still haven't managed to improve their health through weight loss.
Now that you've been properly congratulated for your superiority, are you interested at all in understanding the complex systems that prevent 100 million Americans from achieving the success you have? Like, any intellectual curiosity at all about a problem that causes untold suffering for almost one third of Americans? That costs literally billions in healthcare costs? About stress, anxiety, access to healthy foods, or the novel mechanisms by which a drug which was discovered through studying the venom of a Gila monster operates on the human gut and brain? Or are you only interested in re-telling the world how you don't have the problem that we're trying to solve?
While I do miss it sometimes, I'm perfectly fine with sparkling water. Sure I'll have soda once in a while, but it's now officially a "treat", and not all that sad about it.
If I ever struggle with weight gain in the future, I see no reason to skip a tool that makes that much easier.
It appears that your major issue is that you are simply angry people are taking a short cut. Which seems odd, why would it bother you how someone lost weight, why not just be happy for them?
I got on GLP1s in January. I went from 6'1 240lb to 209lbs with defined abs benching 405lbs at 46 years old. I've worked out my entire life but never been lean like this. I like eating bread (steak, eggs, toast, ketchup and hot sauce is perhaps the single greatest breakfast in the history of the world. The toast is very important!) and potatoes are freaking incredible (mashed with Worcestershire sauce... bruv).
The bulk of my calories are protein but I generally eat what I want if I desire it. I just desire less of it. I had a roast beef sub from Jersey Mike's today with my kid, it was delicious. Their honey mustard is the bee's knees. I had a medium sub though and not a large.
The only change is now I essentially don't eat after 6pm. I just set that goal and the GLP-1 helped me keep it. The only side effects I have had is lower cholesterol and lower BP and that is while running 700mg of test. I'm going to hop on metformin next month after this cycle and target eliminating the fatty liver markers I have had for the last 20 years.
They work friend, they are good for you and they make people live happier healthier lives.
Embrace better living through chemistry.
Moving to higher elevations in the US causes people to become less fat, so you can do this by moving to Colorado.
https://journals.plos.org/plosone/article?id=10.1371/journal...
um, go out and exercise? compared to your ancestors from a century ago, you live a relative life of luxury. THIS IS WHY YOU ARE FAT. Too much food in, not enough burning calories. So simple. Im sure there are people who are clinically fat, broken metabolism, but there are tens of millions of obese in the USA alone, are they all metabollically disabled? I doubt it
But “just personally do better” doesn’t work very well when applied as a medical intervention (they have tried, and checked, over and over, a hundred different ways), even with lots of follow-up and monitoring, and it also doesn’t appear to be how other countries manage to be skinnier than the US. Between those two things, it really doesn’t look like a viable way to solve the obesity crisis—it doesn’t work when we try it, and it doesn’t seem to be what’s working anywhere else.
Strip out all the signals that let the body know it has enough, and it is easier to overeat.
If I were doom scrolling when Adderall kicked in, the risk is I'd continue doing it for hours.
If some rando internet dude thinks I’m weak or stupid, fine with me. It’s a drug that has improved my life in ways that are difficult to describe.
Something that eliminates all your drives except your sex drive, a miracle drug surely.
Weird that this is not talked about more, but I don't see a lot of ads in general so maybe it is.
Our biology is parsimonious. I'd bet that when our brains first started processing higher-level stresses, it salvaged the hunger pathway instead of engineering something biochemically new.
In a lot of ways these other behaviors are similar, it wouldn’t shock me if it’s a shared underlying mechanism originally to encourage eating a calorie surplus.
No.
> Perhaps it stops the addiction without stopping the general desire to drink with friends.
The anecdotes I've heard come from people who aren't addicted, either.
I no longer get that dopamine rush of the first drink.
Some people go as far as describing it as anhedonia. I kinda get it.
Though many people mention feeling sick as a common side effects, I can very well imagine that they would lose any pleasure from food and drink.
This is going to accelerate when every one and their mother (with industrial capacity) starts making generic Ozempic/Wegovy (Semaglutide) next year due to Canada's patent protection lapse[0].
https://glp1.guide/content/novo-nordisk-patent-protections-l...
https://glp1.guide/content/research-on-glp1-signaling-in-the...
https://glp1.guide/content/research-suggesting-glp1-is-a-bra...
https://glp1.guide/content/are-glp1s-primarily-brain-drugs/
This is the killer feature of Semaglutide and GLP1 Receptor Agonists widely. They were originally commonly thought about as digestion-slowing, and while that is part of it, the real change is that it's a brain drug.
Oh also, on whether people gain back the weight:
https://glp1.guide/content/do-people-regain-all-the-weight-l...
tl;dr - most people (i.e. over 50%) do not.
I wonder if this is for wealthy people
(...who might be the target market - being overweight might be a disease of affluence)
In 2026, patent protections that lapse are going to cause a tidal wave:
https://glp1.guide/content/novo-nordisk-patent-protections-l...
For context, the previous calculus was:
https://glp1.guide/content/patent-expirations-for-glp1-recep...
(~2033 for the US)
Theoretically, the tidal wave of generic Semaglutide wouldn't hit the US or EU due to patent protections there... But see the aforementioned note about capitalism.
Note that there is already generic Liraglutide as well:
https://glp1.guide/content/another-generic-liraglutide-launc...
Tirzepatide (Mounjaro/Zepbound) > Semaglutide (Ozempic/Wegovy/Rybelsus) > Liraglutide
But having any of these available is a step change.
> (...who might be the target market - being overweight might be a disease of affluence)
This might be true on the margin but is mostly untrue these days. The lack of access to healthy unprocessed food and the free time to exercise are becoming increasingly problems for those who are NOT wealthy.
Are there severe side effects that aren't extremely rare? can you provide data on this?
We know for a fact the inverse happens: girl starves herself for years to slim down to become a ballerina, eventually decides it's not worth it and tries to stop being so dangerously thin and... can't. She never feels hungry. Every time she eats she can only stomach a few bites before pushing it away. Just eat ice cream? Instant puke. She cannot gain weight no matter what.
Obviously she broke her metabolic system and she obviously did it through diet.
Yes it's possible for some skinny people to gain weight. But that doesn't mean every skinny person simply can decide to be fat just by eating. It's like climbing Mount Everest for some skinny people to put weight on, even if they really desperately want to.
I don't think the situation with obese people is all that different.
mary jane, marijuana, wacky-tobacky, pot, weed...
There are options around that, but that depends on what's driving your personal energy deficit. What's the job that the weight gain intervention needs to do for you, that whatever you try to eat right now does not? What's motivating your current diet? Are you for example disgusted by swallowing anything at all? Are you more partial to liquids than whole foods? Do you dislike sugar in particular?
No, but a pill can make you want to eat more or fidget less etc.
For the pure fat experience I suggest corticosteroids, lithium or a random antipsychotic. Insulin is also very useful here, but a tad dangerous.
If it has to be muscle mass, then anabolic steroids of course are preferable. But beta adrenergic agonists like clenbuterol also seem to have some effect.
And there are many more.
I literally cannot imagine how this is possible. Don't you feel full? Doesn't your body start refusing to swallow? Doesn't the food turn tasteless and start making you nauseous? 100-200kcal over your BMR, sure, but beyond that?
Throughout history, occasional lavish feasts have been very common in nearly every culture.
And while the person is clearly sick, every loved one tries to help by hoping to find food they can eat. Yet it just doesn't work. I've personally seen feeding tubes put in, to help in this regard.
There's some mechanism involved, and I've often wondered if the body knows food will also feed the tumor and is attempting to starve it. Regardless, the 'switch' is there.
It sounds 'obvious', but I don't think it's obvious that she did it through diet.
No, she picked up a mental behavioral disorder that has nothing to do with her metabolism.
If he overeats he said he feels kinda bad (with heartburn the next day).
(From that perspective:)a miracle cure that allows someone to stop being fat is like an indulgence (in the Roman Catholic sense). It’s a cheat, a shortcut that allows the unworthy to reach a state they do not deserve.
My opinion is to wait long enough to validate there are no long term harms, but beyond that, yeah, adjust the priors, it could be a modern aspirin.
What's your threshold on that? How many years is "long enough"? Trying to calibrate my own sense of risk.
A quick Wikipedia search shows Exenatide was FDA approved in 2005 for diabetes.
Exenatide had been in use since about 2005, and by 2019 had more than a million people on it. Some of those patients have literally been on it for 20 years. It does have a worse side-effect profile than Ozempic (or the more modern GLP-1's like zepbound), but even then the benefits outweigh the risk for those diabetics.
Today it is hard to argue the benefits of modern GLP-1s don't outweigh their risks. They've been extensively tested, the class of drug has been around for decades, and they are used by many millions of people.
I personally lost 120 pounds on Zepbound in a little less than a year. It's been life changing, and anyone who thinks I might be less healthy now is very clearly wrong. Literally every aspect of my life has been greatly improved.
my estimate would bigger than others and I would put it at 30-50years.
I take smoking as a cautionary tale, in the beginning it was pushed as not just a recreational thing but a healthy activity that bring benefits with papers published to sing praises about it. my parents were even nudged by their teachers/doctors/etc when they were young to try smoking.
now we all know that smoking is beyond bad and all that early "research" was just people paid off by big companies to promote it.
We performed the surgical options like stomach reduction before this which come with serious danger for comparison
While i agree the gist of what you are saying, also important to mention that humans started cultivating tobaco when mamoths still roamed the Earth. There was indeed a concentrated pro-smoking publicity campaign by tobaco manufacturers in the 1930s, but it was hardly “in the beginning” of our tobaco use.
Links to these papers? I’ve always been curious because I’ve seen this claim many times, especially on HN but no one has ever managed to actually provide a source on one.
There is no modern-style research touting the benefits of smoking qua smoking. I will grant you there might've been some crank self-publishing something, like some of Aristotle's writings.
But you won't find what we'd consider today an acceptable, reputable form of research saying this.
As an American with a sister with thyroid issues, I can say that is absolutely not true for the majority of Americans. People are mostly sympathetic to those who are not obvious slobs.
Everyone benefits from you being fat. Your doctors, your car manufacturer, food manufacturers, everyone. Except maybe health insurance. But they're not hurt too too much.
There's plenty of doctors and surgeons who wish there were less fat people, because they enormously complicate doing surgery on and managing in hospitals.
I agree, but this isn't how incentives work.
Ultimately, there are billions of dollars at play here that rely directly on obesity. The mechanisms of the market and human behavior transcend moral judgement.
What about everybody that works in liposuction?
They want to "fix you," too.
The car industry is a huge one. Making people drive everywhere means more car sales, more fuel sales, more infrastructure built for more cars. And it also makes you fat as a side effect.
I think there's sufficient reason to believe that "Overweight = bad" is a common standard that at least people hold themselves to.
Maybe once they hear the story, but most people assume every fat person they see is a slob
RFK Jr's "let them eat less" is paradoxically the modern version of "let them eat cake"!
It IS simple to reduce your weight. There are like, two things you need to do. It is, however, VERY hard to actually do those things.
I've always been skinny but for some reason I've gained weight recently. Even with keto, intermittent fasting, tirzeptide, and workouts twice a week I have only lost 5 lbs in months. When I was skinny and forgot to eat, I would feel a little crappy but still could function. Now I begin to feel incredibly depressed, I can't sleep nor focus. This solidified it to me that there's a circuit in your brain that controls feeding and if it's out of whack it'll punish you until you eat. Dieting takes months and no one can go that long without sleep. So it's still a practical problem, its just hard to see if your system is well calibrated.
If you're combining a ketogenic diet AND intermittent fasting AND a GLP-1 inhibitor AND exercise and you're still losing less weight than observed in the Ozempic studies, it's likely that there's more to this story.
Ketogenic dieting does not automatically translate to weight loss. Keto simply makes it easier to reduce caloric intake. It's actually very easy to gain weight on a keto diet due to the high caloric density of consuming that much fat.
> Now I begin to feel incredibly depressed, I can't sleep nor focus.
Honestly if you're having these dramatic negative effects from minor caloric restriction with GLP-1 inhibitors, something else is going on.
"it's so easy"
"it's just calories in, calories out"
"if you eat according to this plan and make sure to get 8 hours of sleep a day, you won't even feel the cravings"
Is stuff that fat people say. They totally buy into it and buy all of the products to help them convince themselves this is true. Then they get disillusioned when it doesn't work, have a crisis of faith, then go to the next fad to get over the self-hatred caused by their failure at sticking to something so easy.
Intermittent fasting is great. It got me from 225 to 165, kept it off for the past few years with no effort (my entire metabolism recalibrated to 165-175, I guess.) I also know people who cry actual tears when they're very late for a meal, or panic. Those people need therapy and/or maybe an injection to artificially lower their appetites to the level where I also artificially lowered my own appetite.
Intermittent fasting is no more natural than injections. Dieting is modernity.
So, yeah, dieting is modern, but so is an abundance of food. Both are equally unnatural.
We also didn't get vaccines for most of history. That doesn't mean remaining unvaccinated is good.
For the record, keto works for me (including bloodwork to prove it) but is unsustainable. My mind is never sufficient compared to when I'm eating normally. It's observable in my work and parenting. Although, last time I was on keto, my cholesterol was through the roof. I went off keto and three months later numbers were back to normal. And I wasn't consuming a shitton of meat and butter or anything. I was pretty close to exactly the right numbers for optimal health. Just...something made the numbers terrible and I've no idea why. Did a re-test to confirm. Same awful cholesterol.
On IF I actually got fatter. Numbers worse. Less healthy. Couldn't exercise as vigorously.
For me, calorie counting works. It's also not sustainable, because with kids you get in a rush and if you have a normal social life you eat at places you can't calorie count.
To stay healthy I just try as hard as I can and exercise (distance running, weightlifting, tennis when I can, which is pretty rare with three young children).
Why is this such a complex concept for so many? I literally cannot think of anything simpler.
There's other zero-calorie foods too, but they tend to cause intestinal discomfort rather than improve it.
Started having sweetened oatmeal for a midnight snack and already I feel better all over.
What you're referring to, is the basic concept of thermodynamic calorie in/calorie out. Yes, you can "just" reduce food and lose weight if you hit deficit numbers.
But if you don't do it correctly, you'll feel like trash, you'll suffer bad cravings, and put yourself in a stressful mental situation for days, possibly putting your job at risk.
You have to:
- Eat less than what you're already eating
- But enough to nourish yourself so you keep being in good shape for your work and hobbies
- Manage hunger
- Make the change sustainable so you can keep doing it for the rest of your life.
It's specially hard when your work is entirely sedentary, you live alone and, ironically, when you have a salary that let's you order food every day.
A lot of people don't have it hard. Maybe because they have someone cooking for them at home, because they meal prep the entire week, or because their work is so physically intensive they can just wing it and burn everything with what they need to do for a living anyway.
If you add extra modifiers like "I want to feel great while doing it" and "I want to lose weight while sedentary" and "I want to continue eating whatever stupid thing I want" and "I need to be able to scroll tiktok for at least 3 hours, leaving no time for cooking", it gets much more complicated.
Side note: LOL at "but if you're craving food you might get fired!!1!" - this is professional victimhood at its finest.
Except your calories are from pop tarts.
If you ate 100 calories of pop tarts every hour you're awake for total of 1800 calories... At the end of the month you'd be fatter.
If you ate 1800 calories of pop tarts once a day in 1 hour, you might maintain weight or loose a little. Maybe.
If you had 3600 calories of pop tarts in a few hour window, and then didn't eat again for 48 hours, you'd lose weight in a month.
Insulin control is 99% of losing weight. Yes thermodynamic blah blah, but unless you pay attention to hormone control that controls metabolism in general, it's not going to work without insane willpower to keep your 'calories out' higher than your body wants.
If you repeated the 3600 calories every 48 hours with beef instead, you'd lose weight like never before.
This is thermodynamically impossible unless your daily calorie use is less then 1800 calories.
What metabolic effect do you expect from raising your insulin levels hourly?
Not that I agree that for a human metabolism meal timing makes much of a difference in energy extraction, but it wouldn't be thermodynamically impossible.
Realize that WHAT you put in can change what energy out is.
If I gave you 1800 calories of vodka at 8am, would your use the same amount of energy during the day, and even make it to your 7pm gym? No.
Ok, well sugar isnt exactly the same obviously, but it can also affect what you do that day, how your body acts, your brain even.
Your energy out gets totally messed with after you have tons of alcohol for obvious reasons. Something similar happens on sugar/spiked insulin levels. Can you willpower through it and increase your energy out by running til you drop dead and lose weight? Sure. But it's not easy.
What's way easier is not having the insulin spike in the first place.
Nobody claims that the quality of what you eat has no effect on you, but every study shows that if you maintain the same calorie intake and expenditure it doesn't really matter how you consume the calories or how you expend it.
To not understand that would mean that while believing some studies, you completely ignore all the studies that have been done on insulin and weight gain.
I agree that you would feel very differently in those situations and it's likely you wouldn't spend the same amount of energy unless you really make an effort to do it.
I don't agree that if you do make an effort to spend the same amount of energy you would have different results with regards to weight loss.
2, that in the face of crazy long term insulin/hormone disruption, people will continue to be just as active as if they had a sane diet of mostly meat and vegetables.
I'm starting to see why everyone is so unhealthy.
You don't even need to do keto or wacky "just meat" diets to handle insulin. Protein consumption prevents insulin spikes for around 1-2 hours after eating. Also, proteins and fats slow down digestion.
Turns out, the good old Mediterranean diet is spot-on for a healthy lifestyle.
But yes, meat and vegetables is basically what I'd recommend. Never pasta or bread or sugar unless you need help gaining weight.
How about: some pasta and bread to enable physical exertion.
My father and I have avoided carbs for a few years now. Can do home renovations, gardening, dirt bike riding, and hikes better than we ever did eating carbs. Unless you're doing long distance hikes/running/hard core sports, I really don't think that's true.
Not true for most people. You need to eat fewer calories, not less food. I counted calories for a few weeks an was very surprised.
This is a touchy topic, but I would like to point out that you're missing the obvious confirmation bias that comes with this observation.
There are many people who modulate their weight by changing what they eat, how much they eat, reducing snacking, meal planning, and changing their shopping habits.
You don't see them among the millions of people failing to lose weight or paying for expensive solutions because they quietly solve their problem.
I'm also not suggesting it's easy, but we should acknowledge that many people do successfully control and modulate their weight through dietary and habit changes. There's a survivorship bias problem that occurs when you only look at the remaining sub-group who has the most difficulty with this.
This is a myth.
When you actually track what these people eat, their daily caloric intake averages out to numbers you'd expect. At best, the difference between "fast metabolism" and "slow metabolism" people in studies comes out to a couple hundred calories per day.
You may witness someone consume 2 pizzas and a soda in one sitting without getting fat, but that person is consuming fewer calories for the rest of the day or the week to offset it.
Some people just only want to eat an amount that doesn't get them fat. They aren't using any willpower or anything, they just don't want to eat more than a healthy amount for them.
I am not one of those people (I am overweight when I eat as much as I want), but I am for other things. For example, I don't drink very often (only maybe 10 times a year) and don't get very drunk when I do. I just don't feel a desire to drink very often. It takes zero self discipline to not drink for an extended period of time because I don't have the desire for it.
On the other hand, many alcoholics struggle mightily to avoid drinking. It takes all their willpower to not drink.
Everyone is different in their ability to avoid different addictions.
So, metabolism is really just an expression of how active we are. Some athletes eat 5-10,000 calories a day just to maintain their weight. Hard working laborers also need a lot more calories than office workers.
Meanwhile, people blame their metabolism as if it's just a trait they can't control like their height. You absolutely can increase your metabolism, just move more. This is also likely a big reason why many people gain weight in adulthood - in school we have weekly gym classes and we spend lots of time running around ad playing with friends etc. Then we grow up and our activity level plummets, but we don't adjust our diet to accommodate our much lower metabolism.
If you construct your argument to exclude the 2 out of 3 people who are not overweight and then point out that the remaining 1/3 is overweight, that's the definition of confirmation bias.
It's also a disingenuous argument because not all of those 40% are actively trying and failing to modulate their weight in any way. Most people just don't care.
For example: weightlifters. It’s standard operating procedure to “bulk up” - periods where lifters overeat to promote muscle growth - and then diet to “cut” weight to drop the fat gained during the bulking period while keeping the muscle. They tend to be extremely motivated individuals though.
This is a strange thing to say. If you do something normal, and you end up in a normal state, why would that be a moral failing? There's no such thing as "overeating". Different people eat different amounts. The same person eats different amounts at different times.
> (From that perspective:)a miracle cure that allows someone to stop being fat is like an indulgence (in the Roman Catholic sense). It’s a cheat, a shortcut that allows the unworthy to reach a state they do not deserve.
This is incoherent. If you believe that being fat is a sin, but that the things you do that make you fat are not sins, then a miracle cure that makes you thin removes the only sin you were committing. You can't be unworthy if you're not fat. In order for a miracle cure to be "cheating", it is necessary that the sin is in the behavior and not the result.
I always thought of this as essentially the same idea as with Civ allowing you different paths to victory.
I think that parent is perhaps confusing it with the sin of Gluttony.
I feel like I've seen and heard more of the opposite: The trend is to avoiding anything that might make someone feel blame for arriving in their situation.
With obesity the trend is to blame some combination of "our food supply", trending science topics like microplastics or the microbiome, and genetics.
I've heard countless people explain to me that dieting doesn't work for them. It's not hard to find people claiming they ate <1000 calories per day and still gained weight. Even Eliezer Yudkowsky, a figurehead of the "rationalist" movement, has written about "metabolic disprivilege" and claimed that his genetics do not allow him to lose weight through dieting. This thinking runs deep.
What's interesting about GLP-1 inhibitors is that they modulate the intake portion of the diet, which shatters these previous notions that some people had "metabolic disprivilege" and simply could not lose weight by reducing caloric intake. They just make it easier to reduce food intake.
> I've heard countless people explain to me that dieting doesn't work for them.
I think you're being a tad reductive – "dieting right now doesn't work for me for reasons I can't control" and "reducing calorie intake will help me reduce weight" aren't necessary contradictory, and don't imply "I'm going to attribute it all to biology/blame it on something general".
Anyway, let me assert the opposite: as a partner of a nutritionist who's talked (with anonymity) about her clients, the majority of the people she's worked with, who struggle with sustainably reducing calorie intake over the course of years, come to dieting with that logic, and _then_ struggle against specific barriers, and _then_ blame themselves. (A recent example: "because of my work schedule I don't get enough sleep, which leads to weight gain and time only for frozen food – on top of my predispositions".)
In that case, GLP-1 inhibitors as an intervention _complements_ the way her clients think about dieting.
I was responding to a comment about Americans blaming others, not dieters blaming themselves.
The concept of "blame" isn't really helpful anyway. The problem I frequently see is that blame becomes something to be avoided, which turns into a game of externalizing the source of the problem, which makes people think the problem is out of their hands.
A similar pattern happens in addiction and addiction counseling, where well-meaning friends and family try to soften the blow by telling the person that the addiction was not their fault, it was the result of their circumstances or bad influences. Addiction counselors have to undo this thinking and find a way to gently get the person to take some ownership of their role in arriving at the problem, which is the first step to having some control over correcting it.
For nutrition, when people convince themselves that they have a hidden metabolic disadvantage that makes caloric restriction not work for them, they're more likely to give up than anything.
I thought EY's point was different. Am I misremembering? I thought it was about not being able to do mental work productively when dieting enough to loose weight(maybe maintain a low weight too, though I do not remember that being mentioned explicitly).
Then it turned into a false dichotomy between the 800 calorie severe calorie restriction or no dieting at all. Then he just started declaring he'd delete any comments that suggested dieting.
Why is it that the people who hate fat people, are the ones most opposed to the treatment that will give them the choice to not be fat? If you hate the obese so much, then do you really want to live in a world where the majority of people are obese? It's like burning down a city to be king of the ashes. Some people can only feel superior if others are suffering for it.
it can be more than aspirin. Such an effect on glucose should, among other things, be affecting cancer, probably in a very positive way.
Cooking 2lbs of ground beef could yield a little over 1500 calories (Source https://www.uhhospitals.org/health-information/health-and-we... )
A tablespoon of heavy whipping cream is 50 calories.
There's nothing incompatible with what you wrote and a 2500 calorie diet.
This confuses a lot of people who associate certain foods with becoming fat, or think that eating fat makes you fat.
It's entirely possible to eat what you described and maintain a neutral weight.
There isn’t any real secret to this: This combination of foods leads to you eating a calorically neutral amount every day.
That’s a horrifying amount of saturated fat per day, though. This is an extreme risk for heart disease.
And over a cup whipped for desert.
But I'm also 6'4".
When I ate the standard American diet I was about 40 lbs heavier than I am now.
I keep hearing this, yet after 13 years of keto my cholesterol is still 100. Being fat is much higher-risk than eating fat.
I'm all for obese people taking Ozempic if they really need it, as well as thoroughly studying its long-term benefits and risks, but the fact that we're at the point of considering medical intervention as the population-wide solution to obesity is an abject failure of policy. Looking at our nutritional guidelines, you'd think everyone in America was an extreme athlete. All we have to do is:
1. Take something like the food pyramid, and put vegetables on the bottom, put fat/dairy/coconut and protein/meat/eggs/soy/mycelium in the next level up, put fruit in the next level up, and put starches and sugars on top. In other words: eat real food, mostly plants, without extreme high-carb macros, and treat fruits as dessert. Reverse the failed policy of demonizing saturated fat, and make this the official dietary recommendations for at least a generation.
2. Provide an incentive structure to use lower-GI ingredients in food products. For example, largely replace sugar with inulin fiber sweetened with stevia and/or monk fruit, and largely replace flour with alternatives made from blends of flax, wheat gluten, and resistant starch; no one will notice the difference. Stop letting Cheerios of all things market itself as "heart healthy", at least with its current formulation.
In this world, people would eat way more veggies because they'd grow up with parents and restaurants preparing them properly (with saturated fat and salt). Even for those who didn't, high fiber fortification of UPFs would provide a reasonable backstop. The low-fat/low-salt era's reframing of healthy food as "bland" is a crime against humanity.
For any fat people we still have after that, sure, put them all on Ozempic. It just shouldn't be the expected default that unmedicated people are fat while the medical establishment shrugs its shoulders and doubles down on half a century of empirically bad advice.
You might be happy to know we replaced the food pyramid years over a decade ago. With MyPlate, a visual representation of what your plate ought to look like when it's healthy. Half fruits and vegetables (mostly veggies), a little over 25% grains, a little under 25% protein (protein and fruits are depicted as the same). Dairy is the smallest of all, as a small cup off to the side.
Totally disagree with your idea that starches (grains + potatoes, I assume was your thinking) as the smallest thing. You say "eat real food, mostly plants" and then exclude fruits and grains. You keep complicating your own rule without explaining the complication.
> demonizing saturated fat
are you a cattle rancher? There is oodles of research that saturated fat is bad for you. Full stop.
Here are some literature reviews:
- https://pubmed.ncbi.nlm.nih.gov/34649831/ (they actually have received funding from the beef industry and yet still agree that it looks like a diet high in SFA is linked to atherosclerotic heart disease)
On the other hand, you have bad faith actors like the ones who wrote this:
- https://pubmed.ncbi.nlm.nih.gov/36477384/ where they argue the anti-SFA crowd is a conspiracy-theory laden, unscientific group. If you read their (laughable) conflict of interest statement, they never once actually say anything about themselves, instead just bragging about how they're producing "revelations [that have] never before seen the light"
I actually am too lazy to pull up more. But keto people love to talk about how it's all a conspiracy. I'm glad it works for you. It obviously doesn't work for humans at large.
No, not particularly. It's fine if you disagree with me, but MyPlate isn't similar to what I'm proposing.
are you a cattle rancher? There is oodles of research that saturated fat is bad for you. Full stop.
You're very confident about this. Are you a potato rancher? I've never personally seen a study which convincingly backed this claim up. What I have seen are plenty of bad studies which conflated "high-fat" with "high-calorie", or otherwise failed to isolate the effects of saturated fats.
Where's the long-term study showing that a diet with ~40%+ calories from non-UPF saturated fats, ~15% or fewer calories from carbohydrates, and an ample supply of green vegetables promotes atherosclerosis relative to a control diet with lower SFAs, higher carbs, and equal calories? Has this even been demonstrated in mice? Has reproducibility been demonstrated? Because I haven't seen it, and not for lack of trying.
But keto people love to talk about how it's all a conspiracy.
I never used the word "conspiracy". I don't doubt the government's policies in this area have been perfectly well-intentioned, but it's nevertheless a fact that we didn't have an obesity epidemic before the government began pushing guidelines that resemble the modern ones upon the 1977 conclusion of the McGovern committee.
If these guidelines and the studies used to justify them are so "obviously" great, it's funny how directly they correlate with the exact opposite of their intended effect.
Another interesting question is where do people go from there? What is the next signal of virtue, I wonder.
They can all agree that they're waiting for the other shoe to drop.
That said, we are at a point where people are overweight enough that getting exercise has its own risks, and taking a medication that allows you to be more active is likely to cancel out some of those downsides. As long as you do both I have no problem with people taking ozempic, mounjaro, etc.
I would prefer if we figured out what other than cultural changes is making everyone have symptoms of inflammatory dysfunctions. There is more than one thing going on. Processed foods, contamination, some microbe that doesn't culture in agar. And it's spreading to more of the world.
And yet we rarely ask or say "maybe I should just eat fewer calories?" Unless you have some other disorder that prevents normal bodily function, that does work (and would be viable I'd imagine for the majority of people being prescribed).
But it requires patience and discipline which are basically non-existent for the majority of the population.
Most people suffer from severe self-delusion to avoid the mental pain of coming face to face with their shortcomings.
As a thought experiment, imagine what you eat per day. Now halve it. Would you be having a good time?
> That does not mean it is easy. If you are already fat, which can happen almost without you noticing by eating 200-300 calories too much a day over a year say, or as a result of some brain malfunction (both have happened to me), then eating the calorie deficit require to lose weight is mentally very hard to to.
You install an app. You honestly track what you eat. Set a goal for how many calories per day. Done.
I've intentionally set my calories at 1,300 per day. Low, yes, but I allow myself to eat over that to satiation. The end result is that I'm still in a deficit relative to my actual caloric needs (e.g., maybe I eat 300-500 extra calories and my daily total rounds out around 1600-1800), so I lose weight.
I've started eating less and tracking calories and I'm losing weight (I'm not even exercising—I sit most of the day programming). Nothing extreme, just a simple mental hack.
I've done this before to the tune of losing 70-80 pounds. Literally just tracking calories and not even really exercising beyond walking. I wasted years on different workouts and diets all just to come back to realizing "yeah if you just eat less calories (and increase your intake of whole foods, not boxed slop), you lose weight."
Much better choice than shooting up with pharma syrup that has god knows what in it that's a ticking time bomb.
I personally hope it's just cultural and sugar/hfcs. Because some alternatives might be grim to reckon with just from a humanistic/grief perspective: https://pubmed.ncbi.nlm.nih.gov/34484127/
Or, some of us older folks have been around long enough to understand that we are, in an uncontroversial and factual way, the long term medical trial, and long term effects found in that trial, along with the eventual market withdrawal, may not show up until 10 to 20 years later, creating a healthy distrust in the money/corporations behind the, sometimes outright crafted [1], early medical trials.
Nonpharmaceuticals
- microplastics
- bisphenol A
- asbestos
- nicotine
- DDT
- fungicides like HCB
- PFAS
Pharmaceutical
- benzodiazepines
- Terfenadine
- Benfluorex
Of the 528 new drugs approved over the period of interest, a total of 22 (4.2%) were eventually withdrawn. Between 3.9% and 4.4% of the drugs approved in each 5-year period were eventually withdrawn (χ2 = 0.04, p = 0.99 for difference among 5-year periods). The median time between approval and withdrawal was 1271 days (interquartile range 706–2876).[0]
By some estimates 7% of US have used semaglutides. That is 24.5M people. That could be 24.5M people who have benefitted but if it turns out that there are long term consequences, that's a lot of people who are now all in that ship together when at least some of those users could have chosen lifestyle intervention rather than chemical intervention. If we take the 4.2% recall rate that gives an EV of 980k people in the US who will suffer adverse effects from semaglutides
[0] https://pmc.ncbi.nlm.nih.gov/articles/PMC4085091/?utm_source...
Benzodiazepines do not have effects that only suddenly show up after 10-20 years of use. The serious side effects/withdrawal show up with a few months of heavy use, sometimes sooner. They’re also actively prescribed (with some appropriate caution), so a really weird one to lead with.
There are actually quite a few drugs still widely prescribed today that cause similar QT prolongation to terfenadine (e.g. quetiapine). The difference is they are for more serious conditions where the other options have similarly serious side effects, and terfenadine has to compete with Benadryl. No reason to have to get periodic EKGs just to keep your sinuses decongested in allergy season.
> Of the 528 new drugs approved over the period of interest, a total of 22 (4.2%) were eventually withdrawn. Between 3.9% and 4.4% of the drugs approved in each 5-year period were eventually withdrawn (χ2 = 0.04, p = 0.99 for difference among 5-year periods). The median time between approval and withdrawal was 1271 days (interquartile range 706–2876).[0]
I’ll give you the benefit of the doubt, and assume that you just didn’t care to read the paper once you assumed it agreed with you and did not selectively quote on purpose. From the same paper:
> Of the 22 drugs withdrawn, 11 first had a serious safety warning and 11 did not (Table 2). The median time between the Notice of Compliance and withdrawal was 1271 days (interquartile range 706–2876).
So, the percentage you quoted was double what we were actually talking about here. On top of that, I don’t think you finished reading what you did quote; the median time to withdrawal was < 5 years, and if you actually look at the table only two drugs with serious safety issues actually hit the 10-20 year range you mentioned.
> those users could have chosen lifestyle intervention
We’ve been trying all kinds of “lifestyle interventions” for a long time, from doctors telling people to exercise to semi-organized campaigns of body shaming. It hasn’t worked for the vast majority of people in practice. So unless you have some actually novel idea here, you’re essentially trying to get people to switch from a drug that works to the power of positive thinking. Good luck with that.
I’m not saying we should take Ozempic off the market but don’t be fooled into thinking that we’re immune to unintended consequences just because we did a few studies (almost all of which were on diabetics with controlled diets).
Also, the drug classes you listed are not great examples. Benzodiazepines don’t fit what we’re talking about at all: it’s common to develop tolerance and get serious withdrawal symptoms from a few months of heavy use. You definitely don’t need to take them for 10-20 years (or even the 8 years since Ozempic was approved) to notice the serious side effects. If Ozempic killed you if you quit it cold turkey, we would already know. Psychiatrists were not unaware of what happened when you took too much Valium back in the 60s when it was first introduced. It’s just that they (and society in general) had an attitude toward risks that is totally alien to modern sensibilities (and to be clear, I think it was bad).
First-generation antipsychotic’s incidence of TD was strongly correlated with dose, which was strongly correlated with having schizophrenia and other mental illnesses involving psychosis specifically (as opposed to other indications like bipolar without psychotic features or major depression). Getting TD later in life but being able to live outside of an asylum (they were still around when first-generation antipsychotics were commonly prescribed) is probably a tradeoff many of these people would have taken, even if they knew about it.
Your replies are unnecessarily aggressive, and you’re not reading comments in a charitable way, or keeping track of the usernames writing them. Nobody is saying this.
Also not sure where your quip about me not keeping track of usernames came from - I responded to specific examples given in each individual comment. They just both happened to bring up benzodiazepines.
>> Also not sure where your quip about me not keeping track of usernames came from
You said "neither were you", but that was djtango's first reply to you:
> I wasn’t talking about non-pharmaceuticals, and neither were you
And the most recent example:
> I also never said we were “immune to unintended consequences”. How charitable was putting those words in my mouth?
I didn't do any of that. It's actually completely unrelated to my comment and how you're presenting yourself.
There is never any reason to be cruel or unkind to people who are overweight, but pretending that it doesn't have negative consequences or is even "healthy for me" or whatever is really harmful.
One thing to watch for is effect size: how big of an anti-aging effect does Ozempic confer relative to other good interventions? Were the subjects doing other solid anti-aging interventions like the Fasting Mimicking Diet (FMD)? If not, the 2 interventions might affect the same pathways with the result that if you are doing FMD, you get no additional benefit from Ozempic.
Fen-phen is particularly interesting here because people reported that not only did it help them lose weight, it gave them more willpower and changed their personalities for the better.
IE, if you're getting weight loss at 1/2 the default dose, you might want to stay there, even if your MD wants you to increase to the default.
[default uses loosely here - people build up from a low dose over the span of weeks/months]
And the weight gain is due to a lack of lifestyle change. The drug just numbs your appetite, so you don't eat as much. If you go off the drug and return to over-eating, yep, you gain the weight back.
I also suspect many people lose the weight too fast and go too far. "Ozempic butt" is a joke for a reason - people loose a bunch of fat, but the massive calorie deficit also means they aren't exercising (no energy, and they probably weren't before the drug either), so they've probably crashed their metabolism.
The first time I tried it I followed dosing guidelines for ramp up; side effects were horrible, didn’t lose much weight, and it just kept getting worse.
Second time, after a few months off, I started at lowest dose and stayed there. Side effects were better to start but ramped up again. Eventually my digestion stopped entirely and I couldn’t eat without pain; that actually was good for weight loss but very unhealthy (e.g. despite being hungry and lightheaded the pain kept me from eating more than 400 calories). Eventually it passed but I couldn’t justify taking it after that.
Basic side effects: exercise intolerance (higher starting rate, much faster increase exertion, chest pain after ~150bpm when previously I could run nearly an hour and go up past 180 without issue), fatigue in the morning (despite essentially maintaining my pre-ozempic nutrition), significant increase in resting heart rate, significant decrease in HRV, and digestive upset (basically alternating diarrhea and constipation).
Many of these side effects are well known, others less so.
Ozempic, when micro dosed, did help reduce hunger and make a weight loss diet easier to sustain, until the side effects got so bad I wanted to comfort eat. But mindfulness and healthy lifestyle are similarly effective without crippling side effects.
Although, you may still have issues. It does just sound like there's something unique about your chemistry. I don't think that many of those side effects are even in the ballpark of normal.
I would worry that the side effects I care about are not the side effects that others report being improved on zepbound.
To make matters worse, even ibuprofen is a scam. I stopped taking it and my headache came right back!
More seriously, if you stick to it the GI issues go away after the first month for most people.
- Patients have about 72 weeks to reach maximum loss, they don't lose any more weight after 72 weeks even on the highest dose.
- Patients appear to immediately gain the weight back as soon as they stop taking it.
It's right in the phase 3 trial outcomes paper:
https://pmc.ncbi.nlm.nih.gov/articles/PMC10667099/
I suspect that this info is intentionally down-played so that it doesn't affect sales.
I'm sure some people are going into this without that knowledge, but people are being told this is a lifetime commitment. What you don't see a lot of is why people stop taking it. There's some cases of people losing and then stopping, but the majority are because insurance is forcing people off of it. Just look at the recent CVS Caremark forced switch from Zepbound (2nd Gen) to Wegovy (1st Gen) in July.
This is something I wasn't aware of, are you on 2nd gen Zepbound then?
My wife has been plateaued at an undesirable weight and has been wanting to try this, however, the VA refuses to support it regardless of the fact she fits their guidelines and requirements to receive it. They recently banned it due to costs.
I prefer her to use Zepbound if we can get it, the question is how? We refuse to use the alternative methods where the drug is hand made to be equivalent to them as that seems very sketchy.
Nobody expects a single does of ibuprofen to cure your headaches for life. Similarly, this doesn't "fix" your biochemistry for life, you have to take it in order for it to work.
Yea, hard to figure out why drug companies keep producing "Faustian bargains" in our current system. What galls me is people assume the best for new drugs instead of forcing the _for profit_ entity to prove it's actually safe and useful.
To the extent that, reliably, the first comment on these posts on Hacker News are some wishy washy anecdotal emotional blackmail garbage that completely obfuscates the point and runs direct interference for these large profitable organizations.
To the extent that it's hard to believe that these posts even on this tiny corner of the internet aren't bought and paid for. We live in a society that cherishes organized crime and denigrates hard work. I would not look forward to "new drugs" in this regime.
> What galls me is people assume the best for new drugs instead of forcing the _for profit_ entity to prove it's actually safe and useful.
That's what the FDA approval process is. They already did that in 2017.
The idea that people might only benefit from something like Ozempic a little if they were doing some other intervention before is irrelevant, because no one is doing those other interventions. Requiring people to suffer before providing useful, known-safe and well-researched medication is silly.
Medication is technology.
I think there were some early incidents that would keep it from becoming a legitimate blockbuster, other sleep aids became more widespread and Quaaludes ended up more for retired people who didn't drive or didn't drive as much any more.
Naturally the condos of South Florida were packed with those type residents like nowhere else.
Mostly the old folks would take the first one and the next day feel like it was more potent than they thought. They were potent and most people wouldn't really need one the next night even if they took it for insomnia the night before.
These patients weren't taking them every night, just the opposite, only occasionally, if ever again when they felt like they really needed it.
One day, after a few years, some wild high-school kid with nothing else but pure rebelliousness and unruly behavior in mind, who will take any pill they find, finds out that grandma has a forgotten bottle in the medicine cabinet with 99 of them still in it.
Tries it and likes it. Tells his friends.
Within a few weeks hundreds of kids were finding vast repositories, selling them for $1 each and that's when they first started flying off the shelf.
They probably cost about $6 a 100 for the prescription at the pharmacy, in 1970's dollars.
Interestingly, they became a blockbuster only after it was no longer legitimate.
This is also when pharma started to jack up their prices on a per-pill basis, before that the medical world was still like it really had never crossed their mind until then.
For a number of years afterward new "patients" started preferring them too, on the black market a renewed prescription yielded over 10x the money the drug company made on the same bottle. Pharma was just cringing about it until they eventually got their skyrocketing underway. Still caught them again with opiates, especially Oxycontin.
Since we have young daughters, that aspect of Ozempic really bothers my wife. Though she would have no issue with obese/diabetic people using it to get healthy.
Personally I do think it is a miracle drug and I'm glad people are getting healthy because of it.
When being fat becomes more of a deliberate choice (due to the drug accessibility) I do wonder how society and society's expectations Will change. Will women be even more pressured to "bounce back" during postpartum? Will the "baby fat" we only get to have during adolescence be eliminated and drop out of the shared experience of growing up?
There's also a lot of concern within the eating disorder community about the potential for abuse, because these drugs are so easy to get a hold of by lying on telehealth (could be argued that I've abused them by getting them when they're not truly necessary).
Thank god for poor regulation. Unironically thank god and may this situation continue.
I also notice people will make note that 'eccentrics' from the 1940s-1950s hated air conditioning but it helps to understand it was a dangerous technology that regularly injured and killed people back then, especially in its earlier days the adults of that period were children during. AC didn't get safe until fairly recently in the 70s, 80s and 90s. It would catch fire or leak poison that killed people in their sleep. Some people just saw it as an unnecessary risk. Same with early fridges. When they leaked, that leak could be fatal as poison or explosion.
It wasnt until later that these technologies got safer and even now today, we consider full anesthesia a last resort and will always try to get away with local or twilight anesthesia because full anesthesia does regularly injure, disable, and kill people. Evolution didnt design us to be trivially "shut off" like this. Injecting us with substances like that will always come with risk.
In other words, a lot of those people weren't mindless luddites, but people who assessed their personal risk and said "nope, not worth it." I think that's perfectly fine.
I'd argue the revisionism of today and the ego justifications of the time were just that, ego protection. Its far easier to say "Well, I'm tough, I don't need that," then "I'm scared of that." The former is rewarded in our individualist capitalist society. The latter is vulnerability and honestly which is often only punished in a society like ours. We see it today with people with limited access and affordability to healthcare in the USA putting off care or engaging in various home remedies, alt-medicine, supplements, or conspiracy-culture-esque pharma drugs gotten cheaply via the gray market.
Disability or death are both incredibly rare side effects in modern usage and do not at all fit any pattern you could attach to the word “regular.”
Ahh. "Trust me bro" science! No, no I don't think I will. I think I will trust the actual data.
> People having side effects and injuries from these drugs post-surgery are just told to "deal with it."
Well, generally once something has already occurred, yes, that is the reality. Just like with my damaged spinal cord. I now have to "deal with it" because you can't go backwards. Also "just deal with it" does not imply a lack of documentation that it occurred.
> but it still involves a great deal of risk
Yes, just not the level of risk claimed. In fact, not anywhere close in the modern age.
> especially when we put people fully under.
I've zero doubt. That said, I've had more generals than 99.9% of people ever will and i'm still alive and injury free so yay for modern medical science.
My main takeaway was that "chemicals = bad" is a better heuristic for a starting point where you then look for exceptions or accept them as the last resort after exhausting other options.
Would you let AI loose on the software of your airplanes or nuclear power plants? Medicine is like a sensible idea that should be ok but is hard to rein in and localise to just the area of effect, we hope that it only makes the change we ask from it but we ultimately can't really say with certainty that it isn't also doing something else
I'm actually generally more surprised that people are so trusting of taking medicines and pop pills like they're candy
People whos primary skill is coding, hate AI coding. No talented engineer hates AI coding. The distinction is this: a coder knows how to use their tools, an engineer knows how to work with people, understands product, process, users, and knows how to use their tools.
Talented engineers hate the HYPE around AI. And those of us old enough to remember sigh and think "This is just dreamweaver all over again". It is ESB's with "drag and drop" workflow tools. AI is just another useful tool that a good engineer can pick up and put down where appropriate.
For instance, being in shape used to (usually) demonstrate discipline. Art or music used to demonstrate attention to craft and practice. Knowledge demonstrated time devoted to study.
This isn't to say that the world is worse with these advances (I'd be hopeless without search engines, and I am grateful that people get to live longer and healthier with semaglutide), but I think a little bit of mourning is understandable: what used to be the fruits of hard work are now a dime-a-dozen commodity.
Putting on weight may demonstrate a lack of discipline or awareness, but those losing weight should not be treated as only undisciplined. Scientific research shows that obesity changes the body in ways that actively work against you when you decide to lose weight. You may be able to loose the first pounds with "discipline", but it becomes increasingly harder the more you lose. Once you have lost a few pounds, the body actively works against you to get back to what it thinks should be the baseline.
The whole rush to get people on the thing feels like an opportunistic pharma grab (because it is). The outcome of those sorts of things is never in favor of the individual or their well being.
One can try to rationally argue their way out of alcoholism being a moral failing, but then one notices that in a similar way they can “whitewash” any other moral failing, and the words lose their meaning completely.
Yet people use these words to mean something, and abuse of alcohol falls under that meaning, and every society in existence has always cautioned against and condemned it.
It doesn't. If thievery is a moral failing, how can chopping off thief's hands resolve it? It does resolve further thievery, but doesn't resolve the moral failing of it.
But we may be using different definitions of moral failing
If it just cures the bad habit without the mental work, then probably it would be more appropriate to view it as a remedy for a disease rather than a temporary band-aid for people who are unwilling to put in the work.
There's also something to be said for gaining the discipline to do it yourself along the way, which may lead to keeping more of the weight off in the long run.
We also don't know what the long term side effects of it will be, if any.
I don't find any of that unreasonable to me. I'm saying this as a type-2 diabetic who could stand to lose a lot of weight.
The first GLP‑1 receptor agonist was commercially released in April 2005, meaning 20+ years. People who often repeat this: If 20-years, and tens of trials, isn't long enough to "know" then where is the line exactly?
Thalidomide by contrast was available for 4-years, Vioxx for 5-years, and Rezulin for 3-years by contrast.
> There's also something to be said for gaining the discipline to do it yourself along the way, which may lead to keeping more of the weight off in the long run.
That doesn't work; we know it doesn't work both from small and large scale studies, and population evidence since 1970s. So you're promoting the same thing we've been doing, and failing at, for beyond all of my lifetime. Feels like a religious belief at this point, rather than following the data and what we know from it (i.e. that objectively does not work, and has never worked).
Is there something new you know that health experts haven't known as Obesity as increase up through 40.3%+ (with overweight being 73.6%+)?
What are the long term side effects of NOT taking it? The article implies it could be early death.
This isn't true
https://glp1.guide/content/do-people-regain-all-the-weight-l...
The rest of the incorrect points other people have basically covered, so won't repeat.
Is teaching the discipline lesson worth the shorter life people would live without this medication? Maybe we could find another way to teach people discipline that doesn't maintain a threat to their health?
> I don't find any of that unreasonable to me. I'm saying this as a type-2 diabetic who could stand to lose a lot of weight.
Gonna be incredibly blunt, but talk to your doctor and get on GLP1s. Take a low dose if you want.
GLP1s are incredibly well researched and effective. Imagine dying of a heart attack early because you refused to properly research effective, low-risk medication that is being used by millions and recommended by professional organizations and doctors widely. Real Steve Jobs energy.
Habits are something you can learn though, and having more discipline helps you form them.
Its just inductive reasoning. Most things are not free, let alone miracles. Nearly everything in life has a cost.
However, we also need to be conscious that this is a very very big business, and given the size of the market, is happy to pour billions into some studies that will demonstrate that it has all the benefits in the world and cures everything. Addressing obesity is a humongous benefit in itself, and helps with all the medical conditions that result from it (which in balance makes most mild side effects irrelevant). I am a lot more skeptical about those dozens of claims that it improves X by Y% (often low single digit). Most medical studies in general are dodgy, show minor benefits on small samples in a massively multivariate environment, which more often than not are statistical noise carefully selected, when the approach don't have outright flaws or fraud.
It's the same with people without mental illness. They often have this "just don't be depressed" attitude.
I've seen the same thing and it's simultaneously depressing and fascinating. I think it's a variation of the just world hypothesis. People think in terms of narratives, and so if something bad happened, there must be some moral or reason that rationalizes it. And if something's just good, there must be some catch or hidden secret.
So we can't have a conversation about the positive effects of ozempic without people coming in by the droves speculating that it's part of some hidden trade-off. Because it feels like doing that even without evidence counts as informed skepticism.
I think the reason why we don't see aliens is that intelligent life isn't sustainable long-term, and there's a long list of reasons why intelligence leads to self-destruction.
And those in politics are not interested in change since because (the cynical part starts here) they are selected / sponsored by billionaires who own the media, or go to politics as a job and not to help anyone but themselves
On a side note storing fat to feed the brain in case of bad times makes sense. In the past there were no convinience stores, nor refridgerators
It's not about "big media", it's about the fact that average voter is an idiot. This a fundamental flaw of democracy.
a) emotional damage
b) heart disease
But we're talking about a pill that can hopefully prevent both, so we don't need to make that choice.
Perhaps it is a "motivator" for people to stop gaining weight by controlling their diet before they are too obese, but once you are obese I think it has mostly negative effects.
Losing significant weight is incredibly hard, and gets harder the more you want to lose. If you have lost 20kg (with great benefits to health) and are still made fun of because you are still above average weight it will have a negative effect and the weight will quickly be gained back
Point being: there are overweight Japanese, despite the existence of the measures Japan takes to avoid it. These are the people I mean that it doesn't work for. And for those people, they don't have to deal only with the consequences of being overweight, they also have to deal with being treated very poorly. You can say it's for their own good, and the it incentives them to better themselves. Regardless, it still sucks for them.
Shaming people into losing weight may work, on aggregate. I'm not entirely convinced it's a good way to go about it, at the individual level.
But to be fair It may be psychological. Eating is a very common coping mechanism and not taking care of your body is a common symptom of stress and depression.
There have been some scandals about "miracle drugs" which bad effects have been found only years after being on the market. And side effects can be crazy: I use D2 agonists which works wonder to handle a prolactinoma (like shrinking a tumor with a simple pill every 2 weeks wonder), side effects of this kind of medication can be different addictions (sex, gambling, purchasing etc.) which is always fun when you're one in a thousands to get it.
Some of us also remember previous weight loss drugs which had similar levels of hype and later got pulled because of really bad side effects.
If I needed to lose 100+ pounds, I'd be at my doctor tomorrow asking for it. The side effects of 100+ pounds are way worse than anything semaglutide might cause.
For people who are using it to lose 10-20 pounds, the tradeoff isn't as clear.
I am cautiously optimistic and hope that semaglutide lives up to the hype. lots of people will benefit if it does.
Imagine kids that want to eat chicken nuggets and sweets and don't want to do any exercise because it's hard or makes them briefly uncomfortable. Then apply that image to people over the age of 10.
When I started gaining weight in the past, I changed my diet (permanently up to this point) and got set on a fitness path. These things greatly improved my life and improved my outlook on life. Somebody who just grabs an injection isn't getting that same change in outlook. They're just handling the symptoms instead of addressing the root cause.
I've been taking it for a few months now and it really does seem like a wonder drug. All the benefits I needed without any noticeable drawbacks. It's weirdly good.
Yah.. The track record for public health related items that have a really rapid uptake after release is not great.
That being said, the fact that we let our society in North America get to the point where something like semaglutides are such a huge deal is something to honestly hate, and I think some of the misdirected hate is really a hatred for that.
I mean, that's because that's literally what they need to believe. A majority of people has been brought up on an incredibly moralized account of human behavior, and if it turns out you can just pour some GLP-1 drugs into the drinking water and basically fix a whole bunch of issues it will become obvious that a therapeutic framing is the appropriate way to look at these things.
For people who live in a world of vices and sinners who have to swear off the devil, this throws a pretty big wrench into the whole story, it's much more than just a drug.
The techno-optimist GLP analogs like solving these things with clean energy and other modern marvels throws a wrench into that story.
[0] obesity appears to be caused by moving downstream/to lower altitudes, and has increased in farm and lab animals at the same rates as humans.
I know people who used anti depressants for a few weeks, while going to therapy and fixing their shit, they were out of trouble in less than 6 months. But I also know people who've been basically been taking pills for their entire adult life with absolutely no sign of getting better, the pills just make them cope slightly with their shitty routine/job/&c. while completely destroying their body and making them numb to everything. Same for ozempic, I know people who think you just swallow the pill and that's it, they still have horrendous diets, drink 800cal stabucks "coffee", snacks on sweets all day long, and they're actually gaining weight...
Another good example would be sleeping pills, take them once a year to fix your jetlag and they're amazing. Take them for 10 years because you can't fix your routineof watching tv shows in bed until 1am and "need" pills to fall asleep quickly, you'll just fuck up your circadian rhythm for good and it'll be 10 times harder to get out of the cycle
If you truly want to fix your shit virtually any tool is good, but if you just want a magic pill without putting any work you're doomed, the main issue is that it's advertised and sold as a magic pill
1. We have to trust the data of for-profit pharmaceutical companies and their trials. They are incentivized to produce optimistic results.
2. It's relatively new (insofar that a lot of people are taking it). Opiates were touted in a similar way until the other shoe dropped. There exists an undefined line in time where I would feel more comfortable.
3. It is/was made of a poison from an animal.
4. The extreme benefits are overwhelmingly in obese candidates. Keto is the same way; I tried it and it was not for me because I am not obese.
I'm actually open to any sort of evidence that will change my mind. No name calling please.
Caffeine is an insecticide.
And the gila monsters have their own circulating serum levels of exenedin-4. It's produced in their salivary glands - it's a component in their venom, yes, but they also ingest it themselves, particularly when eating.
But these are fundamentally analogs to our own hormones that have been tweaked to increase desirable properties. It's not like we isolated some random compound that our body has never had to deal with before. (Not that I think that that would necessarily be an indicator we shouldn't use it, either. I don't see why any of this is a strong argument to you, even if your understanding was correct.)
Humans did not evolve for an environment where food is overly abundant and physical activity is optional. For almost the entire evolutionary history of humans, this just wasn't the case. But it is what humans are having to deal with today.
Now, take a look at the "metabolic syndrome" and its prevalence. Clearly, there's a lot of room for improvement.
By all accounts, this generation of GLP-1 agonists has found a meaningful way to improve on that baseline. The benefits are broad and the side effects are manageable. This isn't "surprising" as much as it is "long overdue".
Did you read the abstract? It "reduces aging" in a highly selective group of people with accelerated aging from secondary effects of obesity.
> people with HIV-associated lipohypertrophy disease, a condition characterized by excess fat accumulation and accelerated cellular aging
What's next? "Ozempic shows anti-gravity effects in humans"?
Yes it makes you less hungry, no that's not a solution to the underlying issue of economically induced, nationwide shit nutrition and the enevitble overeating and health issues that ensue.. it's a dodgy crutch.
There are a lot of side effects, of this type of medicine - many which were not really prevalent when it was prescribed on-label.
Metformin, insulin, many vaccines, some statins, and some antibiotics are clearly on that list.
specifically, is what i said.
If you would like to give me money i would be happy to do the research on what claims have been published about GLP-1 inhibitors since they became prescribed off-label.
I assure you it's more than "many conditions downstream of [...]", unless you want to concede that mental health like depression and dementia are related to gut bacteria, then we can be friends.
also, i caught wind that by December 2025 it's going to be recommended / "proven" to work for erectile dysfunction. At a certain point, we're mincing words.
You have no way to assure that and haven't even made that assertion. Depression and dementia are absolutely related to digestion, gut bacteria (as you mentioned), metabolism, and hormones, all of which are affected by GLP-1s.
Also, if someone starts taking GLP-1's (which has a placebo effect to begin with), loses weight, exercises more, and sees improvement in their diabetes, why wouldn't they also see improvement in their depression?
eg https://journals.plos.org/plosone/article?id=10.1371/journal... finds it reduces anger in men but increases it in women.
That's just not true at all. Like, not even close.
Almost everything we've invented in medicine has been free. As in, little to no downsides and just makes things better. And not just in medicine - look around you, compare it to 100 years ago. A lot of stuff is safer, for free.
Think about infant mortality. We went from 1/4 100 years ago to 1/1000s. For free. Surely birth must be more painful now, right? No... we got rid of the pain too. Well surely mothers die more, right? No... They die orders of magnitude less too. Well surely the Vitamin K shot must have SOME downside? Pretty much no, it just pevents bleeding out.
But usually when someone says panacea they don't actually mean a cure-all. Because, obviously, that's impossible and will always be so. They mean something with lots of uses and no downsides.
Also broad-spectrum antibiotics can cause havoc to the body. They're amazing of course, don't get me wrong, but far from a panacea and there are issues in their use and overuse, some of which we're still learning about despite it being a century (in only 3 years!) since their initial discovery.