> However, the study authors emphasize that more research is needed to confirm these mechanisms and determine whether the survival benefit observed in this real-world analysis represents a direct anti-cancer effect or an indirect result of improved metabolic health
Given it’s an observational study, I would bet on the latter. It’s really hard to know you’ve controlled for all confounding factors, and there’s a strong null hypothesis because we know that losing weight can have huge and wide-ranging health benefits.
Yeah, most GLP-1 benefits (or even adverse effects, like muscle loss) seem to be caused by the weight loss. We already knew obesity massively increases risk from a host of diseases, but GLP-1s are still treated with scepticism of the "oh but what about the side-effects we don't know about?!" variety?
> The cardioprotective effects of semaglutide were independent of baseline adiposity and weight loss and had only a small association with waist circumference, suggesting some mechanisms for benefit beyond adiposity reduction.
I'm a big fan of intermittent and water fasting. Have seen things in my blood work that doctors would require me on meds to reverse. Outside of that, I can't speak to the positive impacts on my mood, and general ability to focus.
The simplest solution to a lot of problems is consuming less with the assumption that, most of us (maybe not you), have a lot of spare energy sitting around.
A lie that we don't unlearn as we grow up is we "require" three meals a day. This is true for children who need obscene amounts of energy to grow, but, not for us desk-bound adults.
In the end, giving the body a break to heal by fasting or just consuming significantly less is going to leave more resources for the body energy to deal with other things.
An interesting FYI is a comment made by Peter Attia on his podcast.
He had a patient with metabolic markers that were not improving and they had exhausted all the typical avenues. Presumably they were things like weight loss.
They put the patient on GLP-1 but injected into the thighs (or butt, I don't recall) for the metabolic benefits without the hunger blunting effects.
It seems like GLP1, even in skinny patients (implied by Attia in this particular case), has metabolic benefits.
The longevity community seems to be hinting that there may be geroprotective aspects of GLp1 as well, so we may be looking at the benefits beyond weight loss for metabolism.
Awesome insight. It's not the disability I have, it's that I have never tried healing by fasting. Of course. Because my body was always busy trying to eat food instead of fixing and regrowing all the malformed tissue. Because that's how it works. When a person without legs starts to fast, the legs will suddenly develop.
It would be sensible for you to examine and interrogate why reading a general and fairly anodyne opinion about what might be a solution to a problem some people have led you to interpret it as a prescriptive and judgemental suggestion about the specific problem you specifically have.
I am on GLP-1 (very low dose), and I’ve found that it seems to help me moderate my alcohol consumption as well. Maybe some thing like that could also be contributing to the effect.
I hypothesize that the appetite-suppressing effect of GLP-1 agonists contributes to the normalization of dopamine signaling in the brain. By mitigating the exaggerated dopamine fluctuations seen in food and sugar addiction, GLP-1 may promote a return to dopamine homeostasis, thereby reducing compulsive or addiction-like reward-seeking behaviors.
They have a lot of anecdotal, observational, and emerging RCT evidence on their effects on substance consumption and abuse.
The biggest effect and best tested is on alcohol use disorder. Mechanistically we don't know if it's through some complex reward mechanism, or something simpler like "alcohol is a calorie and you consume fewer calories." The JAMA study showed that GLP-1 reduce Heavy Drinking Days (>2 drinks/day), but did not reduce overall drinking days. This would imply the simple mechanism -> it's hard to drink a lot of calories even if you do enjoy a drink.
More anecdotal evidence showing this effect in opiates, but nothing in an RCT yet.
So far, nothing has worked in stimulants. Cocaine and Meth abuse are insanely difficult to manage therapeutically right now.
I’m about to go to the cinema so I can’t find you references, but there’s a lot of anecdotal evidence at least of glp1’s curbing all sorts of addictive behaviour. I personally started Mounjaro last week and my coffee cravings have gone way, way down for the first time in my adult life.
I believe there is, I don't recall the source but have read that these drugs work by reducing cravings. So they have shown at least hints that they can work on any addictive behavior, not just overeating.
Maybe I'm just an aging cynic, but I'm waiting for the other shoe to drop when it comes to GLP-1s. There have been so many claims of positive benefits that it almost seems too good to be true. With them being so expensive, the producers have every incentive to upsell using any study they can get their hands or money on.
I am sort of in your boat in seeing what may come. There are a few very rare conditions but the benefits seem to out weigh (ha, I will take the pun!) The down sides.
While it might mean the incident rare of some things goes up, those that it reduces are far more impactful and where far more likely to have mortality issues. Sort of like how Chemotherapy is poisonous but potential has better long term odds, only chemo is far more extreme than GPL1.
Time will tell but so far it is looking kind of good with a few lesser issues.
There have been some. I've heard about eyesight related issues. A quick google found this article [0] where results showed that people using GLP-1 drugs were 68.6 times more likely to develop certain types of vision problems.
This is also an extremely rare vision problem. So absolute numbers are very tiny. The absolute numbers for diabetes, weight related problems, etc far dwarf this.
Right. On the whole I think these things are incredible.. looking to try myself after reading here in HN the other day about it working for all sorts of distractions. Just wanted to point out it's not all sunshine and rainbows which would certainly be suspicious.
A lot of the issues are hydration-related, and I wouldn’t be surprised if the eye ones are, too. Some water intake is from food, so if you eat less, you need to drink more. If you also tend to drink with food, and you’re eating less, you may drink less instead of the more that you need to be. Add in a generally dulled “I crave something” sense and you’ve got a recipe for not just going all day without eating, but also without drinking.
Getting people to eat more broccoli is almost entirely upside. Sure a handful of people will be allergic or whatever, but on a population level some interventions are just one positive after another, and there's no reason it has to be a deal made with the devil.
Actually there is a very real effect on which foods you find appealing and which ones are kind of gross. It’s a thing the food companies have been studying, and their own studies show that people on GLP1s tend to skip the junk food aisle and head towards the produce section instead.
I can confirm that. On GLP-1s (when they worked for me, anyway), I'd routinely think "pizza? Bleh, so fatty, I'd really like some chicken breast with roast potatoes instead right now".
GLP-1s have been peescribed for like 20 years, but have been limited more to diabetics and extreme cases. So there is pretty good data. Not to say there isnt going to be side effects in some population sample, but we need to compare that with obesity and diabetes (which is a very bad disease).
I don’t know. Having listened to a number of interviews with some of the founders in this area of drug research I came away with a much higher respect and significantly less cynicism toward big pharmaceutical. Novo Nordisk is run by a nonprofit even.
> Maybe I'm just an aging cynic, but I'm waiting for the other shoe to drop when it comes to GLP-1s. There have been so many claims of positive benefits that it almost seems too good to be true.
Well, read up the testimony of those who stopped taking it for adverse effects, such as nonexistent intestinal transit and -yuck- sulfur burps.
Several members of my family are into glp-1 both for glucose control and for weight loss. Taking different brands (wegovy, ozempic and others.) They all mention.th terrible secondary effects when you eat something "forbidden" (tacos, cake or icecream e.g.) .
Also It causes constipation apparently, which for most of them is not that much of an issue, but given that I've IBS-C, I'm happy to not have to take it.
I'm sure there will be negative side effects but the main outcome of these drugs is that you eat less. Many of us have trained ourselves to eat at a frequency and volume way beyond what is really required to keep our body functioning. This leads to weight gain in most people and thus is the focus but even independent of weight there are effects of continuously eating poor quality foods which are unlikely to be good. So I'm not surprised that there are all these miraculous sounding positive side effects to drugs which prevent most people from putting their metabolic system under near constant load.
When the side effects are better understood I suspect for the average person, eating less would be a net benefit to their overall health - _even if they don't lose any weight_.
Most medications have negative side effects because otherwise our bodies would already have whatever changes they make through evolution. My personal theory (based on nothing but my own intuition) is that GLP-1s are an adaptation to the modern world that evolution hasn't caught up with yet.
And we know what the adaptation is: calorie constraint. We evolved in a calorie constrained environment. We don't live in one now. Our set point for desire to eat is clearly too high. None of this means that glp-1 inhibitors don't have other side effects, of course.
I’m sure some negative effects will be found but from what I understand lowering your weight outweighs (no pun intended) a lot of possible side effects. Closest thing to a miracle cure and quality of life improvement
The fact is though that but-for taking the drugs a lot of the folks that take these things would be long dead before, say, the GLP-1 induced cancer kicked in.
> I'm waiting for the other shoe to drop when it comes to GLP-1s
We know there are downsides. They’re just irrelevant compared to being obese. (Or alcoholic. Or, potentially, overweight.)
It might be a vitamin, where there literally aren’t any downsides. I’m sceptical of that. But to the degree there is mass cognitive bias in respect of GLP-1s, it’s against them. (I suspect these are sour grapes due to the drugs being unreachable for many.)
My frank concern is we’re separating into a social media addicted, unvaccinated and obese population on one hand and a wealthy, insured, disease free and fit one on the other. Those are dangerous class and physical divides to risk becoming heritable (socially, not genetically).
GLP-1’s should make you less concerned in that case, they’re poised to become extremely affordable very soon. Ending the obesity epidemic will do more to bridge the class divide than anything I can practically imagine. Not to mention the other compulsions these drugs help moderate - alcohol, tobacco, gambling etc. It’s my best hope for worldwide quality of life improvement in the next 10 years.
My opinion has shifted over the years. At first I also thought it was largely just sour grapes re: accessibility and fear of the unknown, but now I’m thinking that a large number of people are going to be so far deep into anti-GLP opinions and hot takes they can’t backtrack out of it. Much like political or social beliefs you make into your identity. Too embarrassing to admit you might be wrong.
I know you’re alluding to the same thing, it’s just interesting to me someone else in the world seems to share these thoughts. I also think it may really delineate a multi-generational class divide that is hard to break.
Or all the folks on GLP-1s will develop some rare form of cancer and die early leaving the world to the so-called haters.
Yeah I stopped because I didn't like the way it made me feel. I needed it because my blood sugar was way too high and it helped me drop close to 60 pounds in 6-8 months, but I did not like how it made me feel and I lost more muscle than I was happy with.
I've gained about 15-20 pounds back, but I'm now much healthier overall.
I like how my brain works and I didn't like something affecting or changing that because I couldn't put the fork down. Easy decision for me
Given all the potential money, if they are issues, I expect it to go down like tobacco companies back in the days actively suppressing undesirable research by harassing researchers, influencing peer review journals or/and funding research casting doubt on the benefits of this drug. Chances are that any negative effects won't be obvious until it's too late. Look at microplastics, they have been around for just over a century and it's only now that we are starting to realize that they have several negative effects.
GLP-1s are just showing what people always knew to be true but was not clinically actionable — most of our health problems come from eating too much and being fat.
Well, now it's actionable. No magic, just adherence.
Haven't you been reading Hackernews for the past 10 years? Sugar has been implicated in pretty much every major late-life disease, and the closest thing to a cure before GLP-1 agonists was fasting.
Same. I think that pharmaceutical industry is lot more bleak now than it was when Fen-Phen became popular. GLP-1 usage is largely off-label as far as I know, but I wouldn't trust them even if it wasn't. There is a mountain of precedent for these companies to choose profit over health, and for our government(s) to aid them in covering up evidence of negative effects on the latter for the sake of the former.
The popularity of these drugs is specifically from the FDA-approved "weight loss" indication. You're at least a few years behind. I would also think the many many years when it was only prescribed for diabetes would have yielded some data about negative effects, (other than the ocular issue) if there were any. Glp-1s were so unprofitable, Novo Nordisk let their Canadian patent lapse almost a decade ago, rather than pay the upkeep fee lol. So I dont think anyone is protecting them from bad press.
I do not like the framing. GLP-1 drugs help people lose weight, and it is the weight loss that lowers death rates in colon cancer[1]. This is making it sound like the drug itself is reducing cancer.
There may be some herbal supplements that impact GLP-1 release to some extent, but what is being talked about here are synthetic GLP-1 receptor agonists.
GLP-1 agonists? Well they derived them from a lizard, so, uh… sort of? But no, no foods you eat are really going to have GLP-1 agonists in them, not to any meaningful degree anyway. Plus if you’re eating them they have to survive at least part of the digestive tract, which means you need even more since some of it’ll be lost.
Your body produces GLP-1, but it lives in the blood for like minutes. The innovation was finding a chemical that tickles the same receptors but survives in the body for days at a time.
Private people invested a lot of money to develop this and get it through testing. Allowing them to reap the benefits from their investment for a limited time is just fine.
It's not people couldn't also: Diet, exercise, choose veggies, eat more fiber, etc
Protecting it before generic is fine, but the pricing doesn't make sense.
If it's $1000 per month cost per person when it's the name brand, how many people are on it? At this point just the diabetics and people with really good insurance?
Wouldn't they make a hell of a lot more money selling it for $100 during their protected period to 1000x the people.
No, it is not. They said that since someone, which is typically a fictive person, had spent a lot of money, they deserve to restrict physical persons' access to supposedly life saving substances.
I would like to know how far they take that position.
The standard for medical interventions usually isn’t “could it work?” or “should it work?” but “does it work?”
This is why the efficacy of every single contraceptive method isn’t way higher than it is. Lots of them should work almost perfectly… but the harder they are to use correctly, the less effective they in-fact are.
Eating less, exercising more, has worked for the entire existence of human race. In fact, it worked for me just fine too. GLP-1s are a safe and proven tool and should be used wherever appropriate to assist people. Both of these are simple facts that aren't in contradiction with either other.
But saying the patent owners shouldn't be allowed to reap the benefits of their investment is ridiculous, especially when it's completely possible to lose weight in other ways. 6 years isn't that long to wait anyway.
if you saw the 60 Minutes on compounding pharmacies, which are completely unregulated and never inspected, and sometimes contaminate products out of lack of care/repercussions
you'd never touch a compounded pharmacy product ever again
Compounding pharmacies are regulated by section 503 of the FD&C act, and also subject to inspection.
Are you referring to the fact that the FDA does not inspect all facilities because they have limited resources? This applies to pharmaceutical companies as much as it does to compounders. If you think the FDA posts inspectors at every pharmaceutical company in India, you’d be wrong.
I use that to help me stay asleep. I also feed large amounts of it to horses and deer before, during and after 4th of July since everyone here launches mortars from their fields. Helps them chill.
> However, the study authors emphasize that more research is needed to confirm these mechanisms and determine whether the survival benefit observed in this real-world analysis represents a direct anti-cancer effect or an indirect result of improved metabolic health
Given it’s an observational study, I would bet on the latter. It’s really hard to know you’ve controlled for all confounding factors, and there’s a strong null hypothesis because we know that losing weight can have huge and wide-ranging health benefits.
Yeah, most GLP-1 benefits (or even adverse effects, like muscle loss) seem to be caused by the weight loss. We already knew obesity massively increases risk from a host of diseases, but GLP-1s are still treated with scepticism of the "oh but what about the side-effects we don't know about?!" variety?
Source?
There’s growing evidence of cardioprotective effects independent of weight loss.
Eg https://www.thelancet.com/journals/lancet/article/PIIS0140-6...
> The cardioprotective effects of semaglutide were independent of baseline adiposity and weight loss and had only a small association with waist circumference, suggesting some mechanisms for benefit beyond adiposity reduction.
They also help with slowing the progression of CKD
https://www.kidneyfund.org/treatments/medicines-kidney-disea...
Agreed.
I'm a big fan of intermittent and water fasting. Have seen things in my blood work that doctors would require me on meds to reverse. Outside of that, I can't speak to the positive impacts on my mood, and general ability to focus.
The simplest solution to a lot of problems is consuming less with the assumption that, most of us (maybe not you), have a lot of spare energy sitting around.
A lie that we don't unlearn as we grow up is we "require" three meals a day. This is true for children who need obscene amounts of energy to grow, but, not for us desk-bound adults.
In the end, giving the body a break to heal by fasting or just consuming significantly less is going to leave more resources for the body energy to deal with other things.
An interesting FYI is a comment made by Peter Attia on his podcast.
He had a patient with metabolic markers that were not improving and they had exhausted all the typical avenues. Presumably they were things like weight loss.
They put the patient on GLP-1 but injected into the thighs (or butt, I don't recall) for the metabolic benefits without the hunger blunting effects.
It seems like GLP1, even in skinny patients (implied by Attia in this particular case), has metabolic benefits.
The longevity community seems to be hinting that there may be geroprotective aspects of GLp1 as well, so we may be looking at the benefits beyond weight loss for metabolism.
Awesome insight. It's not the disability I have, it's that I have never tried healing by fasting. Of course. Because my body was always busy trying to eat food instead of fixing and regrowing all the malformed tissue. Because that's how it works. When a person without legs starts to fast, the legs will suddenly develop.
It would be sensible for you to examine and interrogate why reading a general and fairly anodyne opinion about what might be a solution to a problem some people have led you to interpret it as a prescriptive and judgemental suggestion about the specific problem you specifically have.
I am on GLP-1 (very low dose), and I’ve found that it seems to help me moderate my alcohol consumption as well. Maybe some thing like that could also be contributing to the effect.
I hypothesize that the appetite-suppressing effect of GLP-1 agonists contributes to the normalization of dopamine signaling in the brain. By mitigating the exaggerated dopamine fluctuations seen in food and sugar addiction, GLP-1 may promote a return to dopamine homeostasis, thereby reducing compulsive or addiction-like reward-seeking behaviors.
They have a lot of anecdotal, observational, and emerging RCT evidence on their effects on substance consumption and abuse.
The biggest effect and best tested is on alcohol use disorder. Mechanistically we don't know if it's through some complex reward mechanism, or something simpler like "alcohol is a calorie and you consume fewer calories." The JAMA study showed that GLP-1 reduce Heavy Drinking Days (>2 drinks/day), but did not reduce overall drinking days. This would imply the simple mechanism -> it's hard to drink a lot of calories even if you do enjoy a drink.
More anecdotal evidence showing this effect in opiates, but nothing in an RCT yet.
So far, nothing has worked in stimulants. Cocaine and Meth abuse are insanely difficult to manage therapeutically right now.
Is there evidence for addiction tendencies in general? Or is it something specific to alcohol?
A Brain Reward Circuit Inhibited By Next-Generation Weight Loss Drugs - https://www.biorxiv.org/content/10.1101/2024.12.12.628169v1.... | https://doi.org/10.1101/2024.12.12.628169 - December 17rd, 2024
Glucagon-like peptide 1 agonist and effects on reward behaviour: A systematic review - https://www.sciencedirect.com/science/article/pii/S003193842... | https://doi.org/10.1016/j.physbeh.2024.114622 - Physiology & Behavior Volume 283, 1 September 2024, 114622
GLP-1 for Addiction: the Medical Evidence for Opioid, Nicotine, and Alcohol Use Disorder - https://recursiveadaptation.com/p/the-growing-scientific-cas... - May 14th, 2024
The central GLP-1: implications for food and drug reward - https://www.frontiersin.org/journals/neuroscience/articles/1... | https://doi.org/10.3389/fnins.2013.00181 - Front. Neurosci., October 13th, 2013
I’m about to go to the cinema so I can’t find you references, but there’s a lot of anecdotal evidence at least of glp1’s curbing all sorts of addictive behaviour. I personally started Mounjaro last week and my coffee cravings have gone way, way down for the first time in my adult life.
I don’t know! Think I’ve seen a headline somewhere, but can’t remember where. Quick search should help you :)
To me, it’s anecdotal, of course, but I have same sense of being in control over alcohol intake as food intake.
Basically makes it much easier for me to avoid binging.
I believe there is, I don't recall the source but have read that these drugs work by reducing cravings. So they have shown at least hints that they can work on any addictive behavior, not just overeating.
Maybe I'm just an aging cynic, but I'm waiting for the other shoe to drop when it comes to GLP-1s. There have been so many claims of positive benefits that it almost seems too good to be true. With them being so expensive, the producers have every incentive to upsell using any study they can get their hands or money on.
If it's all upside, then I'm happy to be wrong.
I am sort of in your boat in seeing what may come. There are a few very rare conditions but the benefits seem to out weigh (ha, I will take the pun!) The down sides.
While it might mean the incident rare of some things goes up, those that it reduces are far more impactful and where far more likely to have mortality issues. Sort of like how Chemotherapy is poisonous but potential has better long term odds, only chemo is far more extreme than GPL1.
Time will tell but so far it is looking kind of good with a few lesser issues.
There have been some. I've heard about eyesight related issues. A quick google found this article [0] where results showed that people using GLP-1 drugs were 68.6 times more likely to develop certain types of vision problems.
[0]: https://www.aao.org/newsroom/news-releases/detail/do-glp-1-d...
This is also an extremely rare vision problem. So absolute numbers are very tiny. The absolute numbers for diabetes, weight related problems, etc far dwarf this.
Right. On the whole I think these things are incredible.. looking to try myself after reading here in HN the other day about it working for all sorts of distractions. Just wanted to point out it's not all sunshine and rainbows which would certainly be suspicious.
A lot of the issues are hydration-related, and I wouldn’t be surprised if the eye ones are, too. Some water intake is from food, so if you eat less, you need to drink more. If you also tend to drink with food, and you’re eating less, you may drink less instead of the more that you need to be. Add in a generally dulled “I crave something” sense and you’ve got a recipe for not just going all day without eating, but also without drinking.
Even with an increased risk of mortality, at least right now I can live. The voice in my head that is constantly telling me I'm hungry is quiet.
Without it I'd die sooner anyway.
It's not even "I'm hungry", it's just "must have more food". What a nuisance.
Exactly. Food noise is a terrible nuisance. “Go eat.” “Umm, I don’t feel hungry.” “Doesn’t matter, eat anyway.”
Having that on a repeat loop is no fun. Getting rid of it is worth all of the mild side effects and cost.
100% agreed. It would be nice if I lost some weight, but just not having the food noise is worth it.
Many Americans drive a car every day, even though ~40k people a year die in car accidents. Why? Because the benefits outweigh the risk.
(my partner is on a GLP-1, and lost ~25 lbs in 3 months)
> Why? Because the benefits outweigh the risk
Many of us wish we didn't have to drive a car. Many of us also wish we didn't live in a world where hyperprocessed foods weren't the norm
> Many Americans drive a car every da
Coincidentally also a factor of why many Americans take GLP-1 frugs
Not everything has another shoe to drop.
Getting people to eat more broccoli is almost entirely upside. Sure a handful of people will be allergic or whatever, but on a population level some interventions are just one positive after another, and there's no reason it has to be a deal made with the devil.
Well glp1 doesn't make you want to eat broccoli. Just less in general
Actually there is a very real effect on which foods you find appealing and which ones are kind of gross. It’s a thing the food companies have been studying, and their own studies show that people on GLP1s tend to skip the junk food aisle and head towards the produce section instead.
sure but it definitely makes carbs specifically disgusting in my case
I can confirm that. On GLP-1s (when they worked for me, anyway), I'd routinely think "pizza? Bleh, so fatty, I'd really like some chicken breast with roast potatoes instead right now".
GLP-1s have been peescribed for like 20 years, but have been limited more to diabetics and extreme cases. So there is pretty good data. Not to say there isnt going to be side effects in some population sample, but we need to compare that with obesity and diabetes (which is a very bad disease).
I don’t know. Having listened to a number of interviews with some of the founders in this area of drug research I came away with a much higher respect and significantly less cynicism toward big pharmaceutical. Novo Nordisk is run by a nonprofit even.
> Maybe I'm just an aging cynic, but I'm waiting for the other shoe to drop when it comes to GLP-1s. There have been so many claims of positive benefits that it almost seems too good to be true.
Well, read up the testimony of those who stopped taking it for adverse effects, such as nonexistent intestinal transit and -yuck- sulfur burps.
Several members of my family are into glp-1 both for glucose control and for weight loss. Taking different brands (wegovy, ozempic and others.) They all mention.th terrible secondary effects when you eat something "forbidden" (tacos, cake or icecream e.g.) .
I take a glp-1 and suffer no ill effects when I eat something "forbidden".
I'm sure there will be negative side effects but the main outcome of these drugs is that you eat less. Many of us have trained ourselves to eat at a frequency and volume way beyond what is really required to keep our body functioning. This leads to weight gain in most people and thus is the focus but even independent of weight there are effects of continuously eating poor quality foods which are unlikely to be good. So I'm not surprised that there are all these miraculous sounding positive side effects to drugs which prevent most people from putting their metabolic system under near constant load.
When the side effects are better understood I suspect for the average person, eating less would be a net benefit to their overall health - _even if they don't lose any weight_.
Most medications have negative side effects because otherwise our bodies would already have whatever changes they make through evolution. My personal theory (based on nothing but my own intuition) is that GLP-1s are an adaptation to the modern world that evolution hasn't caught up with yet.
And we know what the adaptation is: calorie constraint. We evolved in a calorie constrained environment. We don't live in one now. Our set point for desire to eat is clearly too high. None of this means that glp-1 inhibitors don't have other side effects, of course.
> Most medications have negative side effects because otherwise our bodies would already have whatever changes they make through evolution.
That's not what evolution is, at all
lol
I’m sure some negative effects will be found but from what I understand lowering your weight outweighs (no pun intended) a lot of possible side effects. Closest thing to a miracle cure and quality of life improvement
These drugs have been around for more than 10 years. If there were significant downsides, we probably would have seen them already.
The fact is though that but-for taking the drugs a lot of the folks that take these things would be long dead before, say, the GLP-1 induced cancer kicked in.
> I'm waiting for the other shoe to drop when it comes to GLP-1s
We know there are downsides. They’re just irrelevant compared to being obese. (Or alcoholic. Or, potentially, overweight.)
It might be a vitamin, where there literally aren’t any downsides. I’m sceptical of that. But to the degree there is mass cognitive bias in respect of GLP-1s, it’s against them. (I suspect these are sour grapes due to the drugs being unreachable for many.)
My frank concern is we’re separating into a social media addicted, unvaccinated and obese population on one hand and a wealthy, insured, disease free and fit one on the other. Those are dangerous class and physical divides to risk becoming heritable (socially, not genetically).
GLP-1’s should make you less concerned in that case, they’re poised to become extremely affordable very soon. Ending the obesity epidemic will do more to bridge the class divide than anything I can practically imagine. Not to mention the other compulsions these drugs help moderate - alcohol, tobacco, gambling etc. It’s my best hope for worldwide quality of life improvement in the next 10 years.
> Ending the obesity epidemic will do more to bridge the class divide
My hope is the "waiting for the other shoe to drop" folks are just expressing sour grapes.
If it runs deeper and merges with the anti-vaxers, we've got a behavioural problem fuelling a class divide. That is my fear.
I’ve thought about this a decent amount.
My opinion has shifted over the years. At first I also thought it was largely just sour grapes re: accessibility and fear of the unknown, but now I’m thinking that a large number of people are going to be so far deep into anti-GLP opinions and hot takes they can’t backtrack out of it. Much like political or social beliefs you make into your identity. Too embarrassing to admit you might be wrong.
I know you’re alluding to the same thing, it’s just interesting to me someone else in the world seems to share these thoughts. I also think it may really delineate a multi-generational class divide that is hard to break.
Or all the folks on GLP-1s will develop some rare form of cancer and die early leaving the world to the so-called haters.
I wonder if you could ask: are there downsides to losing weight?
Hey some of us struggle to eat enough and/or remember to eat in the first place
Its not upside per se, more like avoiding the downsides of diabetes and obesity.
Healthy, non-obese individuals likely aren't seeing these "benefits"... But I'm not a doctor, I just pretend to be one on the Internet.
Some people stop using it due to personality changes.
Yeah I stopped because I didn't like the way it made me feel. I needed it because my blood sugar was way too high and it helped me drop close to 60 pounds in 6-8 months, but I did not like how it made me feel and I lost more muscle than I was happy with.
I've gained about 15-20 pounds back, but I'm now much healthier overall.
I like how my brain works and I didn't like something affecting or changing that because I couldn't put the fork down. Easy decision for me
I'd be interested to know how it changed you.
Say more?
I think it's totally fair to be skeptical, but it's also not rare to have interventions that are astoundingly effective.
Antibiotics and vaccines may not be completely free lunches, but they're very good at what they do.
Given all the potential money, if they are issues, I expect it to go down like tobacco companies back in the days actively suppressing undesirable research by harassing researchers, influencing peer review journals or/and funding research casting doubt on the benefits of this drug. Chances are that any negative effects won't be obvious until it's too late. Look at microplastics, they have been around for just over a century and it's only now that we are starting to realize that they have several negative effects.
GLP-1s are just showing what people always knew to be true but was not clinically actionable — most of our health problems come from eating too much and being fat.
Well, now it's actionable. No magic, just adherence.
We don't quite have the data to say "most" yet, but it's certainly looking like "many" is justifiable.
Haven't you been reading Hackernews for the past 10 years? Sugar has been implicated in pretty much every major late-life disease, and the closest thing to a cure before GLP-1 agonists was fasting.
… and the mechanism by which GLP-1s cause weight loss is, more or less, by making fasting really easy.
That's such a lazy and unimaginative take that basically skips 99.999% of human history during which sugar wasn't a problem at all.
The baseline lifestyle of 99.999% of human history would, by modern classifications, be considered intermittent fasting.
That was the part of history when humans didn’t have much access to cheap sugar.
Hacker News has extreme orthorexia and endorses all sorts of quackery.
At this point I view the risks/downsides as akin to vaccines. Sure things happen, the overwhelming positives greatly outweigh this.
Same. I think that pharmaceutical industry is lot more bleak now than it was when Fen-Phen became popular. GLP-1 usage is largely off-label as far as I know, but I wouldn't trust them even if it wasn't. There is a mountain of precedent for these companies to choose profit over health, and for our government(s) to aid them in covering up evidence of negative effects on the latter for the sake of the former.
The popularity of these drugs is specifically from the FDA-approved "weight loss" indication. You're at least a few years behind. I would also think the many many years when it was only prescribed for diabetes would have yielded some data about negative effects, (other than the ocular issue) if there were any. Glp-1s were so unprofitable, Novo Nordisk let their Canadian patent lapse almost a decade ago, rather than pay the upkeep fee lol. So I dont think anyone is protecting them from bad press.
If you eat less your stomach/whole body gets time to relax and repair?
My understanding is that it slows the digestive process, so there isn't more "empty time to repair or relax".
But my thinking there may be naive.
I just know someone who skips breakfast and lunch on the jabs… maybe he eats dinner I’ve not checked.
I do not like the framing. GLP-1 drugs help people lose weight, and it is the weight loss that lowers death rates in colon cancer[1]. This is making it sound like the drug itself is reducing cancer.
[1] https://link.springer.com/article/10.1007/s12672-025-03902-4
I don’t agree. They are not saying that.
It’s observational. They are saying they see correlation.
Your suggested mechanism is plausible, and likely, of course, but that might only be part of the effect.
I think it’s still valuable findings and can help direct further studies.
is there an extract or can you get it from natural food? which have it ?
Resistant starch https://pmc.ncbi.nlm.nih.gov/articles/PMC10085630/ https://pmc.ncbi.nlm.nih.gov/articles/PMC4030412/
There may be some herbal supplements that impact GLP-1 release to some extent, but what is being talked about here are synthetic GLP-1 receptor agonists.
GLP-1 agonists? Well they derived them from a lizard, so, uh… sort of? But no, no foods you eat are really going to have GLP-1 agonists in them, not to any meaningful degree anyway. Plus if you’re eating them they have to survive at least part of the digestive tract, which means you need even more since some of it’ll be lost.
Your body produces GLP-1, but it lives in the blood for like minutes. The innovation was finding a chemical that tickles the same receptors but survives in the body for days at a time.
https://www.sciencedirect.com/science/article/pii/S221112471...
L-tryptophan > Indole > Raises GLP-1
no GLP-1 generics until 2030
lots of people will miss out on benefits, like oh preventing death
our drug system is weird
Private people invested a lot of money to develop this and get it through testing. Allowing them to reap the benefits from their investment for a limited time is just fine.
It's not people couldn't also: Diet, exercise, choose veggies, eat more fiber, etc
Protecting it before generic is fine, but the pricing doesn't make sense.
If it's $1000 per month cost per person when it's the name brand, how many people are on it? At this point just the diabetics and people with really good insurance?
Wouldn't they make a hell of a lot more money selling it for $100 during their protected period to 1000x the people.
They have direct discount programs where they sell at ~ half price.
> Allowing them to reap the benefits from their investment for a limited time is just fine.
Or we could just move to a sane economic system where we don't have to beg the rich/reward people for having money
The public also invested a lot of money.
Kind of weird to assume other people think it's fine to exchange human lives for money.
Is it ethical for me to pay someone to murder you? Does it matter if it costs me a large amount of money or not?
This is a great example of a straw-man attack.
No, it is not. They said that since someone, which is typically a fictive person, had spent a lot of money, they deserve to restrict physical persons' access to supposedly life saving substances.
I would like to know how far they take that position.
"Sorry bro gonna let you die because, muh investments, you see"
Your closing remark is overly simplistic and offers a contradiction: if those things would work for these obese people, they wouldn't need GLPs.
The laws of thermodynamics apply to everyone equally.
Where in thermodynamic principles does it suggest money ought to flow into the pockets of the few?
The standard for medical interventions usually isn’t “could it work?” or “should it work?” but “does it work?”
This is why the efficacy of every single contraceptive method isn’t way higher than it is. Lots of them should work almost perfectly… but the harder they are to use correctly, the less effective they in-fact are.
Eating less, exercising more, has worked for the entire existence of human race. In fact, it worked for me just fine too. GLP-1s are a safe and proven tool and should be used wherever appropriate to assist people. Both of these are simple facts that aren't in contradiction with either other.
But saying the patent owners shouldn't be allowed to reap the benefits of their investment is ridiculous, especially when it's completely possible to lose weight in other ways. 6 years isn't that long to wait anyway.
just want to point out it's not just for obesity
GLP-1 has been demonstrated to even cure some types of long-covid in some people in some cases
and various other diseases
but it's priced way out of reach even for micro-doses until it becomes generic
so all those cases suffer until 2030, if they make it that far, five years is a long time
Compounded GLP-1s are still floating around in the US
if you saw the 60 Minutes on compounding pharmacies, which are completely unregulated and never inspected, and sometimes contaminate products out of lack of care/repercussions
you'd never touch a compounded pharmacy product ever again
people have died from contamination
Compounding pharmacies are regulated by section 503 of the FD&C act, and also subject to inspection.
Are you referring to the fact that the FDA does not inspect all facilities because they have limited resources? This applies to pharmaceutical companies as much as it does to compounders. If you think the FDA posts inspectors at every pharmaceutical company in India, you’d be wrong.
In theory you could supplement with L-tryptophan which is metabolized into indole which then raises GLP-1 production within enteroendocrine cells.
https://www.sciencedirect.com/science/article/pii/S221112471...
It's not obvious that there is a benefit here - the third sentence of the summary at the top says:
> Indole increased GLP-1 release during short exposures, but it reduced secretion over longer periods.
I use that to help me stay asleep. I also feed large amounts of it to horses and deer before, during and after 4th of July since everyone here launches mortars from their fields. Helps them chill.
Or anything that boosts Akkermanskia.