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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 a
by bicx 11mo ago
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.
- piker 11mo agoThe 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.
- bitwize 11mo agoHaven'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.
- phantasmish 11mo ago… and the mechanism by which GLP-1s cause weight loss is, more or less, by making fasting really easy.
- lm28469 11mo agoThat's such a lazy and unimaginative take that basically skips 99.999% of human history during which sugar wasn't a problem at all.
- tengbretson 11mo agoThe baseline lifestyle of 99.999% of human history would, by modern classifications, be considered intermittent fasting.
- jimbokun 11mo agoThat was the part of history when humans didn’t have much access to cheap sugar.
- Der_Einzige 11mo agoYou’re the lazy one.
- ThePowerOfFuet 11mo agoRefined sugar hasn't been a problem for 99.999% of human history because it hasn't existed for 99.999% of human history.
- deleted 11mo ago[deleted]
- pessimizer 11mo agoHacker News has extreme orthorexia and endorses all sorts of quackery.
- robbomacrae 11mo agoThere 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-drugs-like-ozempic-cause-prevent-vision-l https://www.aao.org/newsroom/news-releases/detail/do-glp-1-d...
- phantasmish 11mo agoA 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.
- mock-possum 11mo agoI’m not a doctor but iirc water consumed along with a meal is absorbed slower and therefore results in longer-lasting hydration - than just a bare glass of water on an empty stomach. Of course, eating might add more material that encourages dehydrating, so I don’t know if you’d get a net benefit from a bag of teriyaki beef jerky say.
- azinman2 11mo agoThis 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.
- robbomacrae 11mo agoRight. 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.
- bpodgursky 11mo agoGLP-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.
- degamad 11mo agoWe don't quite have the data to say "most" yet, but it's certainly looking like "many" is justifiable.
- infecto 11mo agoI 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.
- gwbas1c 11mo agoSome people stop using it due to personality changes.
- matthewdgreen 11mo agoSay more?
- ilikecakeandpie 11mo agoYeah 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
- AndrewDucker 11mo agoI'd be interested to know how it changed you.
- CoastalCoder 11mo agoIs it possible that some of that personality change was because you were running a calorie deficit? I'm not dismissing your overall point. I minimize my use of Adderall for that very reason.
- ilikecakeandpie 11mo agoMaybe? I don't think so though. I may have written incorrectly because my personality itself did not change, but it was a massive change seeing eating and drinking remarkably smaller amounts of stuff and I knew it was because of the drug slowing down my digestion. I'd rather have my agency to make mistakes and maybe eat half a pizza when I want to instead of finishing a slice and feeling queasy at the thought of a second one.
- helicalmix 11mo agoI 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.
- ecshafer 11mo agoGLP-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).
- Cthulhu_ 11mo agoBut also do long-term studies; one thing I gathered (anecdotal through the internet so take it with a grain of salt) is that people revert to their old habits when they stop taking it. Not always, of course, and I think using it should always be done with guidance of a dietician etc to make lifestyle adjustments if needs be, but it did imply that long term usage is a factor that needs to be considered.
- hollerith 11mo agoSSRIs have been prescribed for 37 years, and society is just starting to understand that under current prescribing protocols, they do more harm than good. Also, isn't the dose used to treat obesity 3 times higher than the dose used over those 20 years to treat diabetes?
- OptionOfT 11mo agoEven 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.
- stavros 11mo agoIt's not even "I'm hungry", it's just "must have more food". What a nuisance.
- rootusrootus 11mo agoExactly. 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.
- stavros 11mo ago100% agreed. It would be nice if I lost some weight, but just not having the food noise is worth it.
- radial_symmetry 11mo agoMost 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.
- ammon 11mo agoAnd 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.
- lm28469 11mo ago> 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
- dillydogg 11mo agoThis sounds like the argument during the pandemic, "If masks work, then why didn't we evolve permanent masks? Checkmate atheists." Though I do understand the impulse that evolution is working towards some unknowable perfection because of how I was taught evolution during high school, that is, of course, not how it works.
- viking123 11mo agolol
- gedy 11mo agoAt this point I view the risks/downsides as akin to vaccines. Sure things happen, the overwhelming positives greatly outweigh this.
- unsupp0rted 11mo agoNot 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.
- cerved 11mo agoWell glp1 doesn't make you want to eat broccoli. Just less in general
- daedrdev 11mo agosure but it definitely makes carbs specifically disgusting in my case
- stavros 11mo agoI 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".
- dfc 11mo agoYou can confirm that GLP1s make "carbs specifically disgusting" and an example of this reaction is that you would have a desire to eat potatoes?
- jesse_dot_id 11mo agoSame. 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.
- topato 11mo agoThe 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.
- CyanLite2 11mo agoIts 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.
- dillydogg 11mo agoThis isn't true, the heart and kidney benefits appear independent of weight loss. I would encourage you to let the physicians speak to these effects instead of making educated conjecture; it is tough to keep ahead of all of the claims about these medications with my patients. https://www.science.org/doi/10.1126/science.adn4128 https://www.science.org/doi/10.1126/science.adn4128
- deleted 11mo ago[deleted]
- toomuchtodo 11mo agoMany 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)
- culi 11mo ago> 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
- toomuchtodo 11mo agoAgreed, but we must operate and decision in the world we live in, not the world we wish we lived in.
- thefz 11mo ago> Many Americans drive a car every da Coincidentally also a factor of why many Americans take GLP-1 frugs
- chrisco255 11mo agoNot really, Americans have been driving cars for over 100 years but the obesity epidemic cropped up in the last 30 years.
- atherton94027 11mo agoPer-capita volume of miles traveled went up by 5x since 1950: https://enotrans.org/article/americans-drove-1-0-percent-more-in-2024/ https://enotrans.org/article/americans-drove-1-0-percent-mor...
- WithinReason 11mo agoIt's still a factor
- 11mo ago
- JumpCrisscross 11mo ago> 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).
- zemvpferreira 11mo agoGLP-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.
- JumpCrisscross 11mo ago> 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.
- phil21 11mo agoI’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.
- DharmaPolice 11mo agoI'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_.
- coffeebeqn 11mo agoI’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
- 45764986 11mo agoThese drugs have been around for more than 10 years. If there were significant downsides, we probably would have seen them already.
- bossyTeacher 11mo agoGiven 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.
- CoastalCoder 11mo agoI agree. I think it's unlikely that negative effects can go unnoticed for very long, but in the short term I'm only like 97% sure we're getting the full story. That said, it's probably certain enough for me to be open enough to using them now, if my doctor recommends it.
- xtracto 11mo agoSeveral 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.
- tssva 11mo agoI take a glp-1 and suffer no ill effects when I eat something "forbidden".
- deleted 11mo ago[deleted]
- icebergonfire 11mo agoMore anecdata, my spouse and I have been on Mounjaro since Jan 2025 guided by private health insurance. I have suffered almost the entire gamut of side effects from the beginning until I tried split dosing twice a week, and even then there’s still the occasional instance of me learning that I should not have eaten that and the following 9 hours are going to revolve around stomach pain. My partner’s journey on the other hand has been smooth sailing the entire time. YMMV, do your own research but definitely double check any search results with your doctor first… lots of urban myths going around. I do recommend it though, I am the healthiest I’ve been in literally 10 years.
- CoastalCoder 11mo agoI'm surprised that tacos are a big deal. I'd have thought that the filling (meat, cheese, veggies, maybe beans) would mostly outweigh the carbs from the shell.
- m463 11mo agoI wonder if you could ask: are there downsides to losing weight?
- MangoToupe 11mo agoHey some of us struggle to eat enough and/or remember to eat in the first place
- PeaceTed 11mo agoI 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.
- CoastalCoder 11mo ago> chemo is far more extreme than GPL1. Which is ironic because someone at Microsoft once called the GPL "cancer".
- thefz 11mo ago> 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.
- 01100011 11mo agoI was in that boat too but with NAFLD and now liver fibrosis despite not eating all that much sugar and having a BMI that is high but partially due to muscle I finally gave in to see if semaglutide will help. Only on week 3 but it's been a rollercoaster. It seems to have quite a broad spectrum of effects. I'm still not sure I'll be able to stay on it but losing 10 pounds is a nice counterpoint to the side-effects.
- mannanj 11mo agoRight. This is what we heard about the COVID therapies. And we all know how that turned out to be little more effective than placebo for healthy non-comorbid people.
- glp1guide 11mo agoBasically, the gastro-intestinal side effects are the biggest issue, along with CVS (not the store) and possibly eye problems. That said, the negative side effects look to be incredibly rare and manageable (including via stopping treatment) -- and the positives are quite tremendous. It's not a magic drug, but it is the first of it's kind with such a skew to the positive on side effects.
- brazukadev 11mo ago> It's not a magic drug It actually is a magic drug. The same way ultra-palatable food is also not natural.
- Der_Einzige 11mo agoThis kind of “it’s too good so it must be bad” thinking is a cancer in our species.
- hollerith 11mo agoI agree. A better response is, "maybe GLP-1 drugs are really great or maybe the drug companies, which spend most of their time and money trying to manipulate opinion (i.e., by bribing researchers and clinicians, which is not illegal) are at it again."