GLP-1 may slow biological aging(universityofcalifornia.edu) |
GLP-1 may slow biological aging(universityofcalifornia.edu) |
Caloric churn is putting the body's systems through their paces - at the very least for everything related to digestion. But really most of life is well described as pieces of a metabolic process.
If as a result of less caloric consumption you’re starving your cells of needed nutrients, maybe that’s the one that degrades earlier.
People believe what they want to believe; evidence has little to do with it.
They simply assign less weight to evidence that does not meet their "narrative or belief."
If I understand it correctly, GLP-1 drugs help people with weight loss. People are more healthy when they're not overweight, and GLP-1s help people get down to a healthier weight. So when we ask questions about do GLP-1s help this or that, isn't there a giant confounding variable here? That being overweight causes a litany of health issues has been common knowledge forever now. Thus, my (uninformed, intuitive) guess would just be that GLP-1s, which cause weight loss, also include the subsequent effects of healthy weight loss.
So why are we surprised then that people going from overweight to a healthy weight slows aging, or betters cardiovascular health as I've seen elsewhere? Aren't these already well-studied effects of healthy weight loss? Shouldn't these positive effects obviously just be attributed to weight loss, rather than the thing that causes the weight loss? And why are there articles about this stuff acting like this is unexpected?
I admit I'm a laymen and I hope don't sound too snide or critical here. I'm just kind of puzzled by this out of genuine curiosity.
The best paper I've seen on this was the recently published and very aptly named:
"Pleiotropic effects of GLP-1 receptor agonists — a narrative review of extra-metabolic outcomes in adults" (2026)
https://journals.viamedica.pl/medical_research_journal/artic...
Basically with glp 1 it seems to be broadly related to the mess of nonsense that has to do with inflammation/immune/cardio stuff - maybe a set of adaptations that made more sense in a world with more infectious disease/food scarcity but less so now, maybe just a grab bag because evolution is stochastic and is not actually survival of the fittest (it's just survival of the things that survive - there could be 10 organisms that are highly adapted to a particular environment and 2 that are not and would be outcompeted and then a rock falls on the 10 and now the gene pool is what it is - evolution doesn't care). So not really surprising that a thing that works via a mechanism we don't super understand against a condition we done super understand has a bunch of impact on other stuff we don't super understand
2. Hunger signalling isn't the only thing GLP-1s do, so no, we should not just assume every effect stems from weight loss alone. E.g. the blood sugar regulation that makes them very effective for diabetes is not purely about weight management.
We have failed blood pressure drugs that turned into boner pills. We have failed blood pressure drugs that reduce social anxiety. In the field of medicine we have a lot of people acting like we understand the body but we don’t know shit. It’s a bit like how physics was “nearly done” before relativistic and quantum physics were discovered. We still don’t know shit. And we are going to kill or fail a lot of people between now and when we can find our asses with both hands.
Citation needed! it's not actually difficult, all you need is calorie deficit and it has been routinely done by bodybuilders, athletes, MMA fighters and movie stars/models and thousands of ordinary members on r/caloriedeficit subreddit or other fitness subs!
> Hunger signalling isn't the only thing GLP-1s do, so no, we should not just assume every effect stems from weight loss alone
Ofc, they also result in an increased risk of gallbladder stones, bile issues, hair loss, and severe loss of lean mass, and we've got actual studies on this.
GLP-1 then addresses factor X, and the problems it causes, including weight gain.
Not that obesity doesn't independently cause problems but very plausible causality runs more than one way.
GLP-1s are being promoted to and used by the general public, who aren't even obese, because GLP boosters push the magical properties of GLP-1s.
Even most obese people do not actually need GLP-1s.
https://www.nature.com/articles/s41467-026-72861-3
It kinda seems like a bunch of markers moved randomly and some of them happened to move together: "In contrast, causality-enriched epigenetic clocks28 AdaptAge, CausAge, and DamAge exhibited directionally heterogeneous and statistically non-significant changes." That gets you a publication but I don't know that I'd bet money on follow-up study results.
Then there are the mental effects, such as people reporting that they lost various addictive habits (gambling, compulsive shopping etc.)
https://www.health.harvard.edu/heart-health/weight-loss-drug...
I get that science has to be thorough, but how is it at all worth writing about that losing weight makes your risk of heart attacks lower? That GLP-1s are involved suddenly makes this news?
Again, not trying to be snide. I'm on the side of science here, but there's gotta be something the scientists are looking at that I'm not.
>Building off this research, Deanfield is the lead author of a new study recently published in the journal The LancetTrusted Source that provides further evidence of semaglutide and lowered major cardiac event risk, regardless of how much weight a person loses while taking the GLP-1 medication.
>“Semaglutide has previously been shown in the SELECT trial to significantly reduce major adverse cardiovascular events in overweight/obese patients with known heart disease but without diabetes,” Chen explained. “This study analyzed the information from the SELECT study, and found that this benefit to cardiovascular health did not depend on how overweight patients were or how much weight they lost.”
>“This interesting finding suggests that the cardiovascular benefits of semaglutide act through a biochemical mechanism not dependent simply on changing the body weight of an individual,” he continued. “This may open up other avenues of research and therapies that could improve heart health.”
https://www.medicalnewstoday.com/articles/weight-loss-drug-h...
This isn't true. Identical people on identical diets will lose the same weight, GLP1 or not.
> and have better biomarkers like insulin sensitivity
(That part is true.)
These scientists, whose job it is to think about this really hard, why didn't they just think of the most obviously obviously thing? I'm sure they didn't!
...
Dude. Come on.
I even asked, explicitly, “what do the scientists know that I don’t?”
I asked despite the question sounding dumb, because that’s what you do when you genuinely want to know more!
If something is true it will survive the scrutiny, requires no appeal to authority.
https://www.ehlers-danlos.com/effective-doses-of-low-dose-na...
Every gram of body weight needs energy to stay alive. If you are in a caloric deficit, you will lose weight until your energy expenditure matches the caloric intake. If you stay in "caloric deficit" forever you will actually starve by definition.
Properly defining what you mean (comparatively low caloric intake without defining it via the current weight) is actually quite tricky, as your height, body composition and physical activities are all inputs to what counts as a "normal" caloric intake.
Interesting, I wonder if someone will do a study where they pair a GLP-1 with tesamorelin to see if there's any synergy there in terms of fat reduction and reduced aging.
And if you don’t have HIV?
Even in the highest-risk scenario (receptive anal sex) the risk is ~138/10,000 per exposure.
There seems some promise at times but I also struggle to see the recent slew of "GLP-1s cure X", where X is seemingly any ailment known to man, as much more than the next Big Pharma gold rush where the profits dwarf any eventual regulatory fines, and taxpayers and real patients are left with the costs.
:)
> data from a...clinical trial of 108 adults with HIV associated lipohypertrophy
:(
I have never seen a user name better fit a hacker news comment.
This also perfectly sums up the whole emotional roller coaster of modern science communication.Oh that could be cool (title)... Hey this might be good work... Fuck thats depressing I will never get this time back.
Medical marijuana was different, though. The negatives were known medically before and after. The push was almost entirely political and on social media. The few places medical marijuana were medically pushed were either for highly specific applications or as a harm reduction measure: Either as an alternative for patients who demanded opioids (medical marijuana isn’t actually a viable substitute for opioids in severe high level pain, but it’s common for patients to demand to be prescribed something “stronger” for lesser conditions and there was a real problem with opioid over prescription at the time) or from the sector of medicine that sees that patients are seeking out drugs anyway and thought this was a better way to control and monitor it. The way it worked out in practice became a laughable loophole where anyone who wants a card can pay $100 for a meeting with a prescriber who will give leading questions until you say the right things to get the card, which wasn’t even what the original medical marijuana proposals were about.
In the medical and research world, there was never an illusion that marijuana was actually entirely harmless and without drawbacks, except for fringe papers and a few politically motivated researchers.
This is one of the most interesting ideas in medicine right now
You probably lost a major chunk of lean mass if GLP-1 is the only thing you used without much diet changes or exercise.
This is new because I actually don’t feel hungry.
not like we can take GLP-1 even if it was affordable
btw soluble fiber helps people naturally secrete more GLP-1 but of course not on the same level as a dedicated drug
may I ask for how long now? are you athletic? have you experienced any muscle loss?
Seriously, in the first week you should feel a bit of nausea at .25mg. After 2-3 weeks you should see something, either weight loss (most) or gain (some).
Or you could be one of those who have no effect, which sucks. I'd go over your process with your provider, from storage to injection.
even one caffeinated corn syrup slurpee that people consume like it's no big deal can be a quarter or more of your daily energy requirement. a few snacks on top of that and that leaves preciously little budget for real food.
https://www.medicalnewstoday.com/articles/weight-loss-drug-h...
How much are the pharma companies paying people to project this nonsense to trick people to take these drugs to make money out of it?
This is the new grift.
The studies being used to claim “dieting is not effective for weight loss” and for boosting GLPs are flawed and demonstrate corruption and intellectual dishonesty!
GLP-1s are tool like a screwdriver but you do not use one to brush your teeth!
They are being over prescribed and abused, resulting in hair loss, bile/gallbladder stone risks, severe loss of lean mass, etc. Studies are already out on this! So why cherry pick satudies only positives of GLP-1s?
Many boosters have suffered 1 or many of these and now want others to suffer as well to further GLP-1 research at expense of general public!
There is a strong GLP booster group. Most people do not need GLP-1s; all they need is a calorie deficit!
The market is filled with "Eat X for weight loss, eat Y for weight gain."
The average person actually does not choose the right strategy for weight loss, which is a "calorie deficit."
But implementing it is not "EASY" until you understand how expenditure, calorie intake, and weight movement work, which is too much work to understand for an average Joe.
But once you understand the "core idea" it becomes very EASY AND SIMPLE!
Let's take something as simple as "calorie deficit."
Being at a calorie deficit itself requires knowing two things:
1. How much you burn in a day (total daily energy expenditure or TDEE)
2. How much your intake is for the day
Deficit = TDEE - Intake
You can do calorie counting for #2. But what can you do for #1?
The average guy does not know how to calculate these properly, let alone judge weight movement, which can move a lot in the opposite direction due to water weight fluctuations that can exceed 1 kg+ of movement a day.
Even GLP-1 users on Triz subreddit agree with this! https://www.reddit.com/r/tirzepatidecompound/comments/1omfgx...
We use neural network to solve #1 problem (solution is given away for free, we make no money!), you can also do it manually using calculation listed here but it won't be as accurate as our neural network!
- Marketing, to learn what / whom / how to sell: “They spend more on TV ads than R&D!”
- Basic R&D: “Look at all the conflicts of interest in this academic research!”
- Commercial R&D: “They’re just looking for ways to extend the patent lifetime of drugs that only exist because of government-funded basic R&D!”
- Back to the shareholders (mostly pensions and retirement accounts): “Billions of stock buybacks for Wall Street!”
What should the pharmaceutical companies with billions coming in from GLP-1’s be spending their money on?
Criticism does not have to mean preventing work, we can be critical especially of work that we find important.
(If anyone reading this feels inclined to say something like "But how would that benefit them?" -- well, if you restrict consideration to things they could do that benefit them, then it no longer seems so unreasonable if all their options look bad to the critically-minded. Maybe they should be doing things that benefit the rest of the world more and themselves less.)
I'll offer cystic fibrosis as an example. Trikafta may as well be a miracle drug. And CRISPR-based gene editing and replacements are being researched that could be an outright cure, as opposed to a 90% cure.
Even though I personally expect them to be readouts of things that don't affect healthspan much, I don't have any more evidence than those trying to work out what they are. I've been wrong before, and also most tech development does not end up living to its promises, but without the investigation we'll never know.
> Big Pharma gold rush where the profits dwarf any eventual regulatory fines
With pharma malfeasance, the penalties are actually big enough, unlike most other fields. Unless you have something particular in mind?
Wonder where GLP-1s will end up
I hear that word and I immediately think of "that" guy that runs the cocktails of additive interventions to "improve" it.
What would you propose instead? Who will do this research, with what funding, and why will they want to do it? And why would we trust that research more than this? Wouldn’t we scrutinize research carefully regardless of the source?
There are multiple alternative systems, as we see in other countries. But they all have tradeoffs and some really only make sense if some international entity is doing research somewhere else under a different set of rules.
This certainly seems like something a national health service (or even insurance company) should be doing in its own interest (in order to direct spending), and wouldn't have any intrinsic bias towards any particular outcome other than an accurate one. The problem is that you need a government that is not also owned by the drug company.
In the US we have an enormous amount of government health care spending that would benefit from more knowledge about the effects of these drugs. There's no reason why we should ever take the drug company's word for anything. The research was likely originally done in an academic setting, and likely largely government-funded. The only reason the drug companies get these drugs from that environment is through corruption.
> The Bayh-Dole Act made a key change in federal contracting procedures that allowed contractors the right to retain ownership of inventions made with federal funding.
I truly, truly do not understand where this mentality that the medical professionals don't encourage lifestyle changes comes from. If you smoke, they will hound you to stop smoking at every single appointment, regardless of what the appointment is for. They will tell you what to eat. They will tell you to eat less red meat, eat less processed food. They will tell you that you need to exercise 30 minutes a day. They tell you all of this, constantly.
That doesn't mean it works, though. You can tell someone to eat less over and over and that doesn't just magically make them eat less.
This is a statistical fallacy where you're only identifying the extreme cases. The average obese person loses 14-20% of body weight. (Remember that the "obese" category is already defined as 20%+ above the high end of the "normal" range.) So the vast majority of people on these drugs just look normal, not skinny or gaunt.
> They also complain of constant nausea and eat like a bird because eating makes them sick
This is a high dose phenomenon. They can and should reduce their dose if it is preventing them from eating enough or being comfortable.
> I worry about ... medical professionals not using it as a brief intervention then steering towards lifestyle changes.
They absolutely do, of course.
This is why anecdotal evidence is pretty bad.
So people who were fat and get to a normal weight, if you've always known them as fat then they look like they've aged a decade or two in a year. People who were totally normal weight (i.e. "overweight" according to BMI, which is associated with a longer lifespan than "healthy weight") end up looking like tuberculosis Romantics because they wanted to look like movie stars (who are often on severe, unhealthy diets that they stop when they're not working.)
Losing weight quickly often loses it badly - think meth addicts. Women lose fat from their breasts and both sexes lose the fat pad around the eyes; I think these are generally stable fat stores that don't really replenish after being used, even if you gain the weight back. It's not specific to GLPs, just quick weight loss. If you'd lost more slowly your body wouldn't have resorted to taking from those places. Now, you have super-deep nasolabial folds and marionette lines.
> lost weight with diet and exercise
You lose weight through diet. You gain fitness through exercise.
Long term? Who knows for sure. Semaglutide has been approved for 9 years. Liraglutide was 2009 and hasn't shown thyroid issues still. Exenatide has been available since 2005.
GLP-1s aren't new and haven't shown widespread negative issues beyond gastrointestinal upset, and that is typically fixed by... drinking more water. The trials in rats have pointed towards potential thyroid cancer risks but those haven't been seen in people.
I suppose we all could wind up with cancer in 10 years or something hypothetically, due to some unforeseen mechanism. But here's my story.
I went from 200lb to 140lbs at 5' 9" over 3 years. I feel great. I don't need to eat 1000 calories before bed just to sleep through the night. I focus better at work. Blood pressure is back to normal. HDL is back to normal. I can run without joint pain. I feel good about myself. I feel comfortable going on dates. I'm not a near-obese shut-in loner that can't be in a caloric deficit without wrecking my sleep.
Unless there are literally fatal side effects, these drugs seem pretty miraculous.
GLP-1s don't.
Also, dieting without feeling hungry isn't new, people have been doing it but only those who truly understand how dieting works. Most people don't.
but that's not really how the risk should be considered.
If your risk is 138/10000 per exposure and you have sex with your partner once a week for a year, that's about a 50% chance of infection overall. (Assuming the infection risks are independent, which they might not be.)
If it's 4/10000 per exposure then that's a 2% chance of infection after a year, which for sure isn't huge but I personally would take an annual 2% risk of getting HIV quite seriously.
(Obviously the "once a week" figure is an arbitrary choice for the sake of simplicity, and I am well aware that some people have a lot more sex than that and some have a lot less.)
https://www.youtube.com/watch?v=dBnniua6-oM
Dr. Gil Carvalho (medical doctor, research scientist, science communicator) debunks parts of Lustig's 30-year-old claims:
https://www.youtube.com/watch?v=vdoDx9dIuNE
Nonetheless, Dr. Carvalho agrees with avoiding sugary drinks:
"We have a lot of recent evidence, recent studies after [Lustig's] talk. The link between soda and weight gain and obesity and other chronic diseases is quite strong."
Drink fewer sugary beverages, consume fewer calories (eat less), exercise, and drink less alcohol.
That puts most Western governments with limited budgets in a pickle, having promised their citizens modern medicine equitably at affordable cost, tax or otherwise.
Bruh, we're not doing this anymore. If weight loss was easy, we wouldn't have an adult obesity rate of 40%. Yes, yes, a handful of extraordinarily motivated individuals can successfully restrict calories to lose weight. But very clearly most people can't.
> Ofc, they also result in an increased risk of gallbladder stones, bile issues, hair loss, and severe loss of lean mass, and we've got actual studies on this.
You're conflating association and causality. They're used by the obese and diabetics, so they're associated with all kinds of things associated with obesity and diabetes. (But the plausible cause is that the 3rd variable is obesity/diabetes.) Loss of lean mass is basically identical to any other similar level of caloric restriction without corresponding resistance training -- if you don't eat enough to maintain muscle mass, and particularly if you aren't resistance training, no shit, you'll lose muscle. (And guess what? It's still better not to be obese.)
I do not agree with this. Those studies being used to push the idea that "diet and exercise failed obese people" are flawed, and I posted a comment on this post explaining all the flaws. You can choose to respond to them instead; I won't copy paste it here.
Weight loss requires a calorie deficit, and the average person has no training or education for this. Why would you expect them to be good at something they've had no education or training in? 40% obesity rate is not surprising when no education/training exists for average person.
We've already achieved guaranteed results within 2–3 weeks for free (we make no money from this) for all of our users for weight loss or gain, with validation from 17,000+ users for free.
If we are just "scammers," how do we make money by pushing this idea?
You can read reviews and testimonials from people.
The method we use is "slight deficit", see this: https://macrocodex.app/knowledge/rethink/adaptive-tdee/ (you can find all citation/research being used to achieve this)
Our solution is available for free to use!
A deficit so small that most users won't even know that they are at deficit!
You know that if i remove 150kcal from your diet, your wouldn't notice? that's like 2 slices of bread. So the hunger suppression will never be a question for vast majority of fat people
150kcal deficit over a year = 7.1kg or 15.6 lbs lost! and 300kcal = 31.2lbs or 14.2kg!! all this without any injection or drug without any exercise or severe loss of lean masss
>You're conflating association and causality.
Same is true when you talk about positives of GLP-1s, most of the benefits actually come from "calorie restriction" and it's very hard to seperate which part comes from where.
It's simple, and people think simple = easy. It's simple, yet very difficult. Walking up 1,000 stairs is also simple, you just put one foot in front of the other until you're up. But it's hard. We know weight loss is hard because of how many people are obese. Most obese people have tried to lose weight many, many times and have failed. If it was easy, they wouldn't fail. Evidently it is difficult, and no other perspective is reasonable.
Why on earth would having no side effects suck? As long as its working (weight loss) then thats the ideal scenario.
Then GLP-1 comes along and we stop fat negativity/positivity overnight.
And the countries that do have such systems are doing so with US pharma companies cranking out drugs. Presumably if they were fully self-contained that system would be much slower but also generate a higher proportion of medically useful drugs, vs patent-preserving lobbying or other shenanigans.
Extremely unlikely, GLP-1 receptor agonists have been on the market for more than 20 years now, exenatide being first used in 2005.
"GLP-1s cause an improvement in cardiovascular health"
if you said
"GLP-1s cause an improvement in cardiovascular health more than as would be expected by equivalent weight loss"
would that be more specific? Is this right?
Controlled by increasingly unfeeling, sociopathic masters, who grow more and more in power. And now also do not age or get sick.
The power those at the top hold far exceeds any king or emperor throughout humanities history.
No, this isn't true.
Even when two people are identical twins eating the same amount of food and doing the same amount of exercise and activities, weight loss will differ because:
Rate of loss of BodyWeight rate is directly proportional to amount of deficit applied!
Deficit = TDEE (total calorie burn of the day) - Intake
If TDEE is not the same, weight loss will differ, regardless of whether the underlying activity level, genetics, or amount of food or everything else is the same.
For more details u can check my post on this: https://macrocodex.app/knowledge/macrocodex/smart-calorie-bu...
>(That part is true.)
Improved insulin sensitivity is associated with lower excess body fat THE MOST and better skeletal muscle metabolic function. Greater lean mass may contribute.
Therefore, if a person on GLP-1 loses more lean mass than one without, they may not actually have better insulin sensitivity.
⎿ You've hit your session limit · resets 2:56am (Etc/GMT+8 · 47°09′S 126°43′W)
/upgrade to increase your usage limit.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.MR...
> Sponsorship of drug and device studies by the manufacturing company leads to more favorable efficacy results and conclusions than sponsorship by other sources. Our analyses suggest the existence of an industry bias that cannot be explained by standard 'Risk of bias' assessments.
And no! It's not unusual, nor does it mean the results are wrong. It just means there's a known bias towards results that favor the sponsor's interests that needs to be taken into account when evaluating the research. Again, that doesn't make it wrong. But it should make you cautious before thinking that a single study (in a very specific sub-population, at that) is necessarily going to generalize. It might. I hope it does! GLP-1's are awesome. But cautiously.
But ok, sure, drug companies bad. Man hn is really turning into Reddit these days.
"Competing interests G.A.M. serves as a research consultant for Merck, GlaxoSmithKline/ViiV, and Gilead. M.J.C. serves as a scientific advisor for TruDiagnostic. V.D. and R.S. are employees of TruDiagnostic. All other authors declare no competing interests."
These are known risk factors. I've never said drug companies are bad. I literally take corporate funding for my own research. But you also don't get to stick your head in the sand and ignore the competing interests that all make the research more likely to show favorable results. Again for those in the back: These results probably _are_ correct! But do they generalize? Will they hold up on replication with a larger population? Do they matter, or is the proxy they're measuring not actually relevant for long term things in humans? Dunno. That's the thing about a _statistical likelihood of bias_ -- you have no idea exactly how to apply it to a single paper other than to say "ok, known possibility of bias, interpret accordingly."
Again, what’s the evidence that this research in particular should be suspect? It looks a lot like all the other research that goes on in this space. Experimenting with biological systems & real humans is expensive, even when you’re mostly doing data collection. It needs funding!
If you ask your child who enjoys video games to stop playing video games and do their homework, and they tell you they don't have any homework, you're silly (trying to use a kind word) if you don't apply far more scrutiny than if they told you that they had an enormous amount of homework that would keep them from playing video games for the next few days.
You don't need evidence to question this. That the reply is convenient is itself evidence. The reply is consistent with someone who is lying in order to play video games. It is not proof.
Sponsorship of drug and device studies by the manufacturing company leads to more favorable efficacy results and conclusions than sponsorship by other sources.
This isn’t that. It’s just FUD in this context. Nobody casts aspersions about Google authors on their latest database query optimizer paper with Stanford.
If you want a CS analogy, the google-co-authored papers about internet policy do get a lot more scrutiny. And rightfully so! That doesn't make them bad -- many of these are written by friends of mine whom I hold in great esteem -- it means we have to be aware of the potential for all of us to be influenced by the money.