GLP-1s are among the most important drug breakthroughs
economist.com
economist.com
I think we need to greet this whole class of drugs with skepticism, if for no other reason than they’re being a pharma companies’ wet dream of a product. The incentives to interrupt their rollout don’t exist.
I’m aware of the wide range of benefits, and understand they may end up saving lives. But skepticism is warranted here.
They have a history going back to the 1970s (50 years) and have multiple FDA approved brands going on 15 years now (Liraglutide - 2009 for the EU, 2010 for the US).
So sure - we're going to get the chance to observe effects that are very hard to tease out prior just because we have a large number of folks taking them now.
But the press talks about them as if they are well studied because... well... comparatively they are.
Basically - even if I agree that caution is warranted here (and I do), your argument can be equally applied to drugs like ACE inhibitors/ARBs, and insulin. Both are which are pretty compelling drugs.
This is categorically solving addiction, obesity, and diabetes (t2 only I believe). I’m very happy to live in a time period where these meds exist.
It does not "solve" addiction, obesity, or diabetes, it helps alleviate some of their effects. Solving would mean addressing the reason you're addicted, dealing with the underlying behaviors that cause most obesity (unhealthy food, too much food, and too little exercise) and type II diabetes.
There are corner cases where some genetic predisposition, or other factor like cancer treatments or injury lead to obesity or diabetes, and for those cases you probably do need an intervention. But this should not be the case for the masses. It is insane to consider "just giving this drug to everyone" especially when some of the side-effects include:
- Hypoglycemia
- Gallstones
- Pancreatitis
- Kidney failure
- Thyroid cancer (maybe)
and often include
- Diarrhea
- Constipation
- Fatigue
- Abdominal pain
- Bloating
- Burping
- Heartburn
- Blurred vision
From an investor's perspective, I'm sure this is magic. From an interventionist medical system like the U.S., I'm sure this also seems magic. But for nearly all people dealing with these problems it doesn't address the underlying behavioral issues.
- adoption of GLPs into diabetes treatment guidelines
GLP-1 is a hormone that is released every time you eat, and the drugs are virtually identical hormones at natural levels that take ~100x longer (half life of a couple hours) to be excreted. It's a tiny amount of one more peptide among millions- that part is certainly safe.
If there's any issue with the drug it would be from the constant activation of a natural hormone receptor. Like how anabolic steroids can hurt you, and TRT can affect your natural testosterone production. Maybe after 10 years it breaks your natural satiety system and makes you always/never hungry. That kind of thing would probably show up in mouse models.
Either way- obesity is the largest cause of lost years in the first world and it isn't close. If you are obese your whole life you die 10-15 years earlier and are sicker. It's not going to kill you as fast as untreated t2 diabetes, but in both cases it would be crazy not to take a drug that can just make those problems just go away.
The long-term effects of diabetes is. For me, this was the _ONLY_ thing that brought my blood sugar under control.
Even with severe dietary restriction, my blood sugar would be dangerously high first thing in the morning after fasting 12-16hrs.
The 'potential side effects' of the drugs that I was taking was terrifying. And the list of drugs that I was on was so long that even if there was only a 1% chance that I'd catch a side effect from 1% of the drugs then my prospects went down to nil.
I was scheduled for gastric-bypass surgery.
I can modestly say that ozempic probably saved my life.
I've lost ~100lbs (~45kgs) and I can now wear the same size clothes that I wore in high-school which is a nice benefit too.
I think it's been around for long enough (2017-2024 for Semaglutide), and there have been enough people taking it (tens of millions), that it's possible to start drawing conclusions about this. Maybe a Bayesian approach might say something?
Now we have to wonder when people are going to try mandating these. I can imagine the argument will be "of course not, covid was killing everyone and contagious. Well, obesity is killing everyone and driving up healthcare costs. But my body my choice! But not when it can harm other people! Etc"
What weight did you start out from? 40-50 kg is what I'd like to lose after all, I think.
To be honest I do the cardio mostly to stay healthy, I am not convinced it contributes much to the weight loss. I had to pause the cardio twice for a week while on holidays and lost the same amount of weight those weeks. I do take vitamins supplements though.
In term of meal, I take some supermarket ready meal, typically pasta. So it's not even an unpleasant diet. But just that for the day, no dessert. I think cutting sugar is key. I do allow myself a glass of red wine in the evening.
Now I am no doctor, I don't necessary recommend it, it is just that it worked for me, and allows to make an intense but concentrated effort. Another downside of a fast weight loss like that is loose skin, will probably take a few more months and some weight lifting to remediate that.
I stopped eating processed foods and cut nearly all my sugar intake. It was a total lifestyle change and I lost 40 pounds in the process. I’ve been off of it for nearly a month, kept off the weight so far, and never felt better.
That said...
For me, I went from 276lbs to 162lbs at my lowest in about 9mo on Tirzepatide (Mounjaro/Zepbound). 85% of the loss was in the first 100 days. I was putting in all the effort I possibly could aside from taking the drug, but I attribute the drug for most of my actual long-term success. It made things I had tried to do in the past (eating healthy, eating properly sized portions, regulating my snacking/late night binges, drinking) much easier. I call it a PED for dieting. Losing the weight also made exercising at first tolerable, and these days downright enjoyable and something I look forward to on training days.
Since I hit my lowest I have put on about 25lbs of lean muscle mass by hitting the gym for resistance training at a regular consistent schedule. When you see the results I did so rapidly in one direction, it's highly motivating to know you can "put in the work" and see results in the other. I'm now about 187lbs at 5'11" with a body fat percentage of just under 12% from my latest DEXA scan. I plan to try to stabilize at around 11% or so, since the studies on it show 12% is where the major long-term health benefits start to accrue. After that I will begin to focus on increasing my VO2MAX (e.g. cardio fitness) as much as possible. I'll be at 2 years from starting Tirzepatide this coming March.
The drug in combination with lifestyle changes can work wonders. I am but one example, and not much of an outlier at this point.
I used to worry about "outing" myself when I first started taking it, but after seeing the results I did and having friends ask me what the hell I was doing to see such success I realized I could no longer pretend it was "eating less and moving more" - I didn't want to be part of the problem.
Hope it helps someone reading this!
* Once the actuaries see the long term data I imagine insurance companies will foot the bill entirely for them as a cost-saving measure. The only thing strong enough to override a doctor's "I bet it's your period" is "I bet it's your weight."
* It is genuinely far far easier to maintain weight than lose it. Your body establishes a new set-point and you +/-10 lbs around it naturally.
Can't speak for these drugs specifically but after losing 100lbs my appetite adjusted, got higher energy, far less effort to do (well everything) but working out especially.
But yeah, that's a good point I suppose. Fewer side effects than meth that's for sure.
Only a conjecture, since as OP said, the long-term effects haven't been studied for us to be so sure.
No it's not. Diet is just what you eat. It can be healthy or unhealthy.
I equate GLP1 hype in the medical industry to AI hype in the tech industry. Yes it's an important breakthrough but there are other much more important breakthroughs that humans have achieved in the past.
[1] https://www.who.int/news-room/fact-sheets/detail/antimicrobi...
With so many people taking antibiotics for their coughs and sniffles NOT caused by bacteria, they end up being more present in sewage, another place that antibiotic resistance increases.
And finally we feed way too much to the cows.
It would have been really, really wise for the healthcare governing bodies to limit antibiotics to hospitals, and stop sending promising new candidates overseas to any country with a track record of overprescribing and not doing a better job of monitoring treatment adherence. It's inhumane for us to allow illnesses abroad to become increasingly untreatable while those governments shrug off the problem. Mandate change in policy before sharing new formulations.
I don’t know if it’s rooted in jealousy over access the drug (either via insurance or having a provider willing to prescribe) or whether it’s because people see those who take it for weight loss as “cheating”.
And then I listed to a few. The stories are horrific.
Most have tried 10+ different diets throughout their life, none of them successful in the long term. They get fat-shamed, discriminated against, insulted.
They go to a doctor for any reason whatsoever, even for things totally unrelated to obesity, and their doctors tell them to lose weight. Either in a very careful and sympathetic manner, or very condescendingly.
Many develop shame, anxiety and anger around the topic.
I've also learned how hard it is to change deep-seated behaviors, especially if your environment isn't really helping, or provides incentives in the other direction.
In the end, most medical intervention are a form of "cheating". Your eyes aren't good? Wear glasses or contact lenses. Your immune system can't cope with these bacteria? take antibiotics. Cholesterol too high? Take a statin (or whatever it's called). Can't control your eating habits and hunger? Take GLP-1s.
We should strive to reduce our moralizing and help those we can help.
I've felt and thought about it the same way for a long time. Especially because the solution to obesity is just so easy: Eat less (and healthier) and exercise more.
It's just so easy, just do it. Why do I struggle with that? Well, probably not disciplined enough. Time to feel bad about that and question everything or at least something...
In theory it is easy, but reality is much more nuanced with job or personal stress, psychic health, impact of your surroundings, your body chemistry being disturbed and whatnot. This medicine seems (so far) to take stress (somewhat) out of it, so I can focus on changing the underlying behaviour without having to worry about calorie counting at the same moment.
But yes, if you stop taking it, and nothing has changed, you will probably bloat up again.
No one is screaming at a schizophrenic to summon the willpower to stop hearing voices, but many certainly will do so to those fighting addictions or other ingrained behavior. This might seem like false equivalence, but they are both abnormal psychological traits, one happens to rely on the environment more than the other.
As another example, some animals will overfeed if you let them, and you can craft super obese animals genetically. No one is damning fat squirrels, screaming "If only they had the willpower to stop overfeeding!"
I think it'll be gone over the next few years as these drugs become more prevalent.
No, it's because you can get the same result, plus other ancillary benefits, by simply stopping the behavior causing the issue.
Imagine smokers rambling they can't stop smoking because bad tobacco put addicting chemicals in their cigs. Just put that shit out already, right? Same for food. Eating for survival =/= the american diet.
Processed food is bad, and everywhere. Ok. What are you going to do, take semaglutide and then eat the same shit, but a bit less? Or are you going to switch to healthier food? Then why don't you switch now and skip taking a medicine for the rest of your days?
GLP1 is a drug to heal the lack of willpower, not to heal the body.
Must be nice to have a metabolic system that works correctly. A lot of us don't.
For too long obesity as a mental fitness issue without considering underlying causes. Too often overeating is considered the cause not the symptom.
For many, our bodies lie, telling us we need to eat because our blood sugar is low, when in fact it's already normal-high but other process is getting in the way of energy production.
And people who are 5'7" can dunk basketball if they "simply" jump higher.
Ok, and so what? If some people lack the willpower of others, and this drug helps them gain that willpower, isn't that great?
You sound like someone telling a clinically depressed person "just stop being sad".
Time will tell. Reducing obesity rates from 50%+ to 10% would put it firmly in that category for me and most others.
2 years or so ago I started telling friends that this class of drug will end up being seen as the most important drug development since antibiotics when held against the impact it will have upon western societies. I still stand by that, even ignoring the supposed ancillary benefits aside from simple weight loss.
The largest negative anyone can point to at the moment is fear of the unknown and the current cost. The latter will resolve itself rapidly - you can already get a weekly dose sourced for less than a cup of coffee if you are feeling a bit more adventurous than most, which suggests the costs will rapidly crash once competition enters the market en-force.
It would be of course far better to change Western diets and lifestyle - but that is basically solving the impossible. This is the next best thing.
Also, marketing departments don't usually do this, they just say "we're the best product in the market" and define best in some ambiguous way.
But what will happen from now on? Will the obesity industry cave, or will they try to fight back and overcome the effects of the drugs with even shadier practices? Option 1 sounds overly optimistic to be honest…
But yes, regulating the food industry would have achieved the same health effect than these “miracle drugs” for much cheaper and less adverse effects… But they are too big of a lobby to be targeted by governments unfortunately.
So you are fighting against big food by rerouting your money to big pharma? What a win...
It…feels…sponsored.
I Totally get that GLP-1's are absolute medical breakthroughs. But they are a _serious_ societal problem, IMO. My partner and I are both larger-bodied people; both our BMI's (it's a terrible measurement, I'm aware) hover just over 30. We've done a lot of work to destigmatize our own bodies and accept who we are so that we can teach our kids to have healthy self-images and not suffer the dysmorphia that we both went through for decades. We're active, we eat well, and we have great lives; we just aren't _thin_.
My partner has a new coworker who just started on Wegovy and has been poisoning my partner's brain with her terrible self talk. She calls herself a "fat bitch" at work, and raves about how excited she is to "lose all the fucking weight" before her wedding next fall, and it's bad enough that my partner has had to talk to her manager and HR about it. It's bad enough that my partner broke down the other day and told me she's struggling to see herself as anything other than overweight and unhealthy because the negative sentiment her coworker has of _her_ body is leaking onto everyone else.
These medications are absolutely essential for _some_ people who need to lose weight for medical reasons or need the other benefits they provide. But, they've also unlocked a cheat code for losing weight, and people like my partner's new coworker are focusing on only that aspect. The potential societal effects of making weight loss easier than ever before are kinda terrifying to me. I don't know what I'll say to my kids if they end up with our body type and come to me one day asking to go on Ozempic or Wegovy because "all the kids at school are doing it" and "being thin is what's normal now". I'm so scared that we've opened up a Pandora's box of making thin even more of an expectation because it's "easy" now.
I guess my point is, I _really_ wish the FDA would step in and make it clear that these medications are not to be prescribed for cosmetic weight loss, and they should bring the hammer down on online pharmacies like Hers (which is where my partner's coworker got her Wegovy).
EDIT: there are a bunch of folks in the replies telling me I'm lying to myself and misserving my kids by accepting myself. That's...odd, to say the least. Every metric I have that isn't my weight is perfectly fine. My blood pressure is normal, my cholesterol is normal, my A1C is normal, my blood sugar is normal, my doctor and I are very happy with my health. The number on the scale is _a_ representation of your health, but it's not the only or even best one. And the impact on my mental health has been astounding. I'm not going to change my mind about my weight because a bunch of folks using an extremely outdated metric of overall health tell me my number is bad.
> We're active, we eat well
Respectfully, you are both obese. If you’re ok with that that’s ok; but to say your diets are appropriate is telling yourself a lie.
That doesn't mean you need to change anything or that you're weak or whatever people might say. I do tons of unhealthy stuff that are fine for the time being. I drink for one - that's gonna catch up to me.
Because muscle is way more dense than fat, and we should factor in for bone mineralization and bone weight in those who do resistance sports as well.
So take BMI = kg/m2 with precaution, as there better metrics such as waist-to-height ratio.
BMI is a fine metric for describing a population's general health when it comes to weight. The actual reason the metric exists.
There are exceedingly few folks with 10% body fat and a BMI of 30. They tend to be clustered around professional athlete or bodybuilder circles. Again, not interesting to discuss these things outside of niche circles. Those that are outliers know already, due to the work they put in to be such.
No one is walking around with a BMI of 30 and happening to accidentally be at a healthy weight due to low body fat percentage/high lean muscle mass and not knowing it.
Excess weight is tied to pretty much every major cause of mortality and morbidity in the west. The UK's plan to offer Wegovy to unemployed people with complex health problems etc is, leaving aside its many political problems, a great illustration of how this is the case.
It may just be that tackling obesity lowers the strain on public health systems to such an extent that it is worth it financially, for those countries that have such systems coexisting with high rates of obesity.
...then it's not cosmetic weight loss? I don't think we disagree. If we prescribed these medications the same way we prescribe, say, blood pressure medication, I think I would be less worried. When you have high blood pressure, they of course put you on a medication immediately to get your blood pressure down, but the goal is to reduce the medication over time by helping you work on the underlying cause of the high blood pressure. Some people just have naturally high blood pressure and will need the medication support forever, and that's OK, but many people can engage in lifestyle changes that will give them most of the improvement they need. If we were approaching GLP-1's with the same mindset I think I would be much less worried about the future of our society with these medications.
And for what it's worth, the above isn't a "coping strategy". It's body acceptance, which has made me a hell of a lot healthier than all the attempts I made at losing weight I didn't really need to lose in order to be healthy and happy.
I stopped eating processed foods and cut nearly all my sugar intake. It was a total lifestyle change and I lost 40 pounds in the process.
I’ve been off of it for nearly a month and I’ve kept off the weight so far.
Unfortunately, evidence so far seems to show sustaining weight after discontinuing GLP-1 RAs isn't very common
But just because some people abuse it doesn’t mean that it should be avoided entirely.
We don't really know the coworker's medical conditions.
Also, I'm not sure that achieving a positive self-image isn't worthwhile. With any drug you take, you balance the positives and negatives. I really don't know the negative side effects of these GLP-1 drugs, but if it turns out the negatives are low and the cost isn't too high, I'm really not sure why we'd want to keep people from using them how they want.
A BMI over 30 is obese, which is unhealthy in and of itself. It’s great that you try to stay active and eat well but you’re not healthy. And I worry that you’re teaching your kids bad lessons.
Being obese is also not attractive, sorry but that’s not going to change.
Obesity is a genuine clinical disease, not a lifestyle inconvenience.
Body image issues are usually very personal and not relevant in discussions about eradicating the disease at a macro level.
Good luck banning this newcomer. At least GLP-1s have health benefits.
I say this facetiously knowing Hacker News doesn't have those features, but what do these posts hope to achieve that hasn't already been achieved?
We'll see some variety of:
- Isn't it all just because of weight loss? Well, read the damn article because the author sure claims at least some effects don't seem to be because of weight loss.
- Isn't it all just because of eating less in general being good for you? If you're overweight, sure. If you're weight stable, seemingly you can't just eat less or you'll eventually starve to death.
- I'm worried about the long-term side effects we don't know about. Well, GLP-1 agonists have been approved for human use as a diabetes treatment for 20 years, so at what point are you expecting these to show up?
- Isn't this an amphetamine? No, it isn't.
- Isn't this addictive? No, it isn't.
- What about all the horrible side effects? The side effect profile for these drugs are among the most mild of all regular use drugs you can take. The few severe effects are incredibly rare and the most common issues with nausea are heavily dose-dependent and tend to go away after a while.
- Don't you need to increase the dose forever? No, you don't. The Ozempic is pretty low and stays low. The Wegovy dose is much higher but still capped, and if you see increasing dosages, it's because of titration to find the needed amount without overwhelming you all at once and taking more than you need.
- Why didn't the body just evolve this itself? The human body, all mammal bodies, and possibly other animals do in fact produce GLP-1. It isn't very long-lasting in serum, though, so medical researchers figured out how to make an analog that won't break down in minutes. That's all these drugs are, something your body already makes but a longer lasting version. GLP-1 is, in fact, secreted in response to eating, and is one of the signals the body produces telling you to stop eating when you've had enough. This mechanism seems to be broken for one reason or another in many people, and those people end up obese. Increasing the level exogeneously seems to help, as you might expect.
Is there anything else that is going to come up? Because it sure feels like the exact same back and forth, every single day.
You say this like the current readers of HN have been here since the beginning and no new readers have come along since then. New readers come along at some rate I have no idea about, but I'm assuming it to be >0% per day/month/year. These new readers will find something existing readers have already seen and post it because it is interesting to them. This is no different than seeing the same "experiments" every year in 5th grade science fairs.
“ That does happen, of course, but research shows that it is not the full story. A study of more than 17,600 overweight and obese patients from 41 countries who took semaglutide found that participants lost about 10% of their body weight and had a 20% reduction in serious adverse coronary events, strokes, heart attacks and all-cause mortality. Crucially, these cardiovascular improvements long preceded any meaningful weight loss. ”
I've heard this one before.
There's a little thing called the opioid epidemic that started because Oxycodone was meant to be free from the potential to be addictive.
30 years later - oops.
I trust medications which haven't become generic less than leaches on any claim they make.
There were a whole bunch of other factors involved outside of a 30 year old marketing slogan.