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.
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.
Literally too much water or aspirin can kill you. Some people are allergic to avocados. Driving kills huge numbers of people daily. Everything is about risk/reward, and looking at the macro picture. And right now the comorbidities for obesity are terrible in huge absolute numbers… something that GLP-1’s can take down in significant magnitude. Unless we learn that the majority of users end up with something worse than obesity, they’re a huge win for public health.
A large drop in HbA1c does cause early worsening of diabetic retinopathy. Regardless of how it's achieved. So expect some noise in generalized data.
Personally, I went from mild background retinopathy to PDR and getting laser treatment in about 3 months. My ophthalmologist (who has an academic background) didn't really know if this diagnosis had the same "quality" of someone who "naturally" progresses to PDR, but some studies say it's transient.
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.
I’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.
It's a little suspicious... 68x risk with semaglutide, no significant risk with tirzepatide. Case-control studies that merely search these databases are only really useful for hypothesis generation.
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).
But 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.
SSRIs 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?
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.
Oddly enough semaglutide is making me crave sugar more. It might be the frequent sensation of having low blood sugar. Idk.
It does make me choose more dense meals though since I know I can't eat that much due to delayed gastric emptying. But I have to budget some room for prunes to counteract the constipation. It definitely makes you think about what you eat.
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".
Oh no, you have torn through the flaws in my argument like bullets through paper, however will I live this down? Unless I clearly meant "it makes previously-desirable food undesirable", anyway.
I was not trying to tear your argument down. The comment you replied to was about carbs being specifically disgusting and in my head potatoes are the runner up to bread for classic examples of carbs. I was simply asking about what seemed like a contradiction. I have been looking into GLP1s and have not seen/heard people mention that GLP1 make carbs gross.
I think it varies per person. For me, it didn't specifically make carbs gross, but it did make unhealthy food less palatable. I think that's what the GP was talking about as well, they were just a bit more specific.
It really depends on the person, though. They worked for me for a while and don't work now, but I'm a small minority, from what I've heard from people. When they worked, they were great.
The automobile's net effect on behaviours has (as others have noted) evolved over that period, as has its net effect on transportation and urbanisation patterns.
Up until the end of WWII, automobile ownership was relatively limited. It was just beginning to accelerate at the beginning of the war (in the US), but rationing and war-time defence manufacturing curbed that trend, and sustained rates of alternative transport, particularly rail.
Post-war, there was a mass-consumer blitz, much of it revolving around automobiles, and changes such as commuter suburbs (based around automobiles), superhighways, self-service grocery stores, shopping malls, and strip-mall based retail development began, all trends which evolved over the next 50+ years.
In the 1970s and 1980s, it was quite common for children to walk or ride bikes to school, or take a school bus (which involved walking several blocks to a nearby stop). Since the late 1990s, far more seem to be ferried in private cars, usually by parents, who spend a half-hour or more in pick-up lines. It's not uncommon for children walking along neighbourhood streets to be reported (and collected) by authorities by concern for their safety, and their parents subject to investigation or worse. Suburban, and even urban development patterns have been to ever-lower-density and far more bike- and pedstrian-unfriendly modes.
Recreational, occupational, educational, and other transport and activity patterns are largely away from self-powered movement (walking, cycling, etc.) and toward motorised options (sometimes including e-bikes, electric scooters, or equivalents, though most often automobiles).
Societal change and consequent impacts take time and have long lags.
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.
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_.
Basically, 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.
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.
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
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.
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.
This 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.
I 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.
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.
I 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.
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 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.
More 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.
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.
This 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.
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.
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 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."
> 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.
Right. 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.
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 it's all upside, then I'm happy to be wrong.