> “The researchers believe semaglutide’s anti-aging properties stem from its effects on fat distribution and metabolic health. Excess fat around organs triggers the release of pro-aging molecules that alter DNA methylation in key aging-related genes. By reducing this harmful fat accumulation and preventing low-grade inflammation - both major drivers of epigenetic aging - semaglutide appears to create a more youthful biological environment.“
In other words, being medically obese ages your body quite a bit, its stresses out your body with inflammation, etc. Taking Ozempic helps people lose weight, which also reduces inflammation. This is sort of like saying we proved rain (usually) increases humidity lol. A very obvious finding.
The article even says “ Randy Seeley from the University of Michigan Medical SchoolView company profile expressed little surprise at the findings” :)
What the people in this study have causes abnormal visceral fat accumulation in the belly and back and itself causes disturbing changes in body shape and appearance, does not respond or normal weight loss, and hasn't had real treatment options. That ozempic has beneficial effects for it in an RCT is actually awesome, it's the framing given by the headline that is bad.
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.
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.
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.
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.
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.
(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.
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?
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.
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.
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.
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.
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.
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.
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, fat/dairy/coconut and protein/meat/eggs/soy/mycelium in the next level up, fruit in the next level up, and 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 guidelines for at least a generation.
2. Provide an incentive structure to use lower-GI ingredients in baked goods and UPFs, e.g. largely replace sugar with inulin fiber sweetened with stevia and/or monk fruit and largely replace flour with alternatives made from flax, wheat gluten, and resistant starch. Stop letting Cheerios of all things market itself as "heart healthy", at least with its current formulation.
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.
Another interesting question is where do people go from there? What is the next signal of virtue, I wonder.
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.
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.
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.
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".
So "try harder" isn't going to work when the doctors don't even know what they're talking about.
I'm losing faith in this forum. People would prefer to give people pharma bs because no processed carbs is too much of an ask. Pathetic.
[EDIT] It's not that your approach can't work, it's that if (for example) people had as hard a time following the directions for condoms as they do following diet & workout plans, we'd never allow condoms to be sold as contraceptives, they'd not even be close to being OK to promote as useful for that purpose. It wouldn't matter if a few people could follow the directions and it worked 100% of the time for them.
Anyway, it does work, people just aren't told to do it firmly. Doctors dance around it.
They're morons for the most part.
In their 8 minute session with you, they are worse than chatgpt basically.
Maybe if the anti-carb society offered some payola, the story would be different.
At most a drug rep comes by and brings donuts or something to talk about their new drugs.
Source wife is a doctor.
https://www.mdlinx.com/article/a-physician-s-guide-to-accept...
Increased reporting requirements and a cap on the value of these gifts that is far too low for box seats.
My wife's a physician, and I've seen these things change dramatically. Sometimes some food for the whole office will get dropped off. Or donuts. No one's getting box seats to a pro sports game anymore.
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.
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?
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.
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.
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.
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.
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.
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.
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.
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.
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?
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.
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.
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.
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.
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.
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.
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.
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.
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.
Its just inductive reasoning. Most things are not free, let alone miracles. Nearly everything in life has a cost.
Yah.. The track record for public health related items that have a really rapid uptake after release is not great.
> The researchers used epigenetic clocks to assess biological aging - sophisticated tools that identify patterns of DNA methylation, chemical tags that affect gene activity and shift predictably with age
It's amazing what lowering inflation, reducing body weight can do to the body. It's almost becoming irrelevant that GLP1 Receptor Agonists were originally for type 2 diabetes (i.e. reducing HbA1c) -- the effects are profound. Kidney health, heart health, overall health, longer lives -- all for the low low cost of gastrointestinal problems (which can be serious, especially if dehydrated).
[0]: https://glp1.guide/content/are-glp1-side-effects-all-the-sam...
In other markets, where it is under patent, it is significantly cheaper than the $500/month or more in the US currently. For example in the UK it is roughly $150/month USD privately (i.e. not through the NHS).
In China it will be out of patent within two years.
Since about 1/4 of the people in the US are on medicaid, close to 90 million, that means the drug manufacturers will probably raise the price for everyone else in the US because they got to get their profits somehow...
https://www.whitehouse.gov/fact-sheets/2025/07/fact-sheet-pr...
If they're serious about this, they would introduce legislation rather than send strongly worded letters to pharma companies.
I gather it's extremely easy and basically fool-proof, as far as producing the desired drug and not producing some other, undesired drug. Much easier than, say, home-brewing beer. The risk is all in contamination, which presents a vector for infection.
[EDIT] I don't mean to downplay the risks or suggest people go do this, only to highlight that there's enough demand for this that we're well into "life, uh, finds a way" territory, and also just how lucky (assuming these hold up as no-brainers to take for a large proportion of the population) we are that these things are so incredibly cheap and simple to make, if you take the patents out of the picture.
My mother, a healthy and active 87-year-old, started taking Ozempic because she was overweight and her doctor was impressed by the drug’s supposed miracles. She ended up suffering from severe intestinal motility issues, went through a lot of pain, and had to be admitted to the ICU.
The long-term systemic effects of these drugs are still largely unknown.
The predecessor of semaglutide, liraglutide has been sold since 1998. GLP-1 has been studied since the 70s. The first human was injected with GLP-1 agonists in 1993 IIRC.
These drugs are not novel, or new and we absolutely know the long term health impact.
The long term effects of obesity are very well known though and unlikely to be better than any still unknown negative effect semaglutide might have.
If you're allergic to peanuts it doesn't mean everyone is going to suffer some huge medical crisis from peanuts in 20 years.
She stopped using the drug and the problems disappeared.
If I lose 20 kilo's, my "biological age" might go down 2 years, but that doesn't mean it's "slowed"
[1] https://trial.medpath.com/news/5c43f09ebb6d0f8e/ozempic-show...
After adjustment for sex, BMI, hsCRP, and sCD163, semaglutide significantly decreased epigenetic aging: PCGrimAge (-3.1 years, P = 0.007), GrimAge V1 (-1.4 years, P = 0.02), GrimAge V2 (-2.3 years, P = 0.009), PhenoAge (-4.9 years, P = 0.004), and DunedinPACE (-0.09 units, ≈9 % slower pace, P = 0.01). Semaglutide also lowered the multi-omic OMICmAge clock (-2.2 years, P = 0.009) and the transposable element-focused RetroAge clock (-2.2 years, P = 0.030).
The podcast is only 3 hours long! The GLP-1 discussion starts at 2:09:53.
[0] https://www.foundmyfitness.com/episodes/ben-bikman
EDIT: ycopilotFYT version https://www.cofyt.app/search/dr-ben-bikman-how-to-reverse-in...
https://glp1.guide/content/semaglutide-vs-tirzepatide-clinic...
My bet is on the reduction in inflammation -- it's a notoriously beneficial positive side effect of GLP1 Receptor Agonists, along with the obvious reduction in weight or HbA1c.
https://glp1.guide/content/a-new-glp1-retatrutide/
Currently the only people experimenting with it are the underground gray market peptide enthusiasts (you can find them on reddit and elsewhere), but the results are quite intense.
https://trials.lilly.com/en-US/trial/580035
As one might imagine though, capitalism found a way. A LOT of compounding pharmacies are now very good at manufacturing GLP1s (not necessarily the case that the knowledge transfers, but I imagine networks/knowledge sharing groups do), so gray market has sprung up to supply adventurous people with Retatrutide.
https://trials.lilly.com/en-US/trial/580035
Just to be very explicit here, my profit incentive is selling newsletter subscriptions not selling drugs, if that was the worry.
The thing is that we just won't get any high quality data from the official trials for a very long time, but it looks like it's going to be even better than Tirzepatide which is the current king.
Outside of being simply well-researched, the best thing about GLP1s is that they are safe enough to be taken by millions of people (and they are) -- so anecdata is valuable. It's valuable to know what the "first adopters" are doing and what they're finding and what trends show up there.
[EDIT] Maybe I'm reading the comment wrong -- to answer with good attempt assumed, I think GLP1s are basically the answer to obesity on any reasonable time frame.
GLP1s not the answer we wanted (most people would have preferred better food ingredient regulation, more people choosing healhtier lifestyles, etc), but it's the solution we're getting, it seems like.
Right now the only thing I think most can do to help this wave along (unless you're a drug manufacturer, insurer, or politician) is to share as much information as possible on positive and negative side effects, how the drugs work, why they work, etc.
That being said, I'm waiting for oral GLP1 agonists. Injections are a hassle and gray market ones even more so
It turns out enterprising chemists and pharmacists are capable of reverse engineering.
I don't think it's that hard to figure out how someone might do it -- imagine having to reverse engineer food you've received, given many samples. Imagine some of those samples might have "fallen off the back of a truck".
> That being said, I'm waiting for oral GLP1 agonists. Injections are a hassle and gray market ones even more so
This is really going to be the second leg of adoption and will catapult GLP1s even further IMO. Rybelsus has not really seen a ton of popularity compared to the injections. That said, Orforglipron is Eli Lilly's upcoming oral GLP1 and it looks to have really good results:
https://glp1.guide/content/updates-from-maritide-orforglipro...
(and if glps don't work well enough to allow this, then maybe the next medicine in the pipeline)
xeromal•13h ago
declan_roberts•13h ago
For cardiovascular health, they see benefits even with people who are at a healthy BMI, which suggests therapeutic effects beyond just losing weight.
xeromal•13h ago
jjtheblunt•12h ago
regardless, thanks too.
Tade0•10h ago
I never went above 25 BMI but I wouldn't call myself a healthy person as it's obviously like that only due to low muscle mass.