6 ms·

The long-term side effects of GLP-1 drugs are not well-studied, but the press seems to talk about them as if they are—in glowing terms as if their broad adoptio

The long-term side effects of GLP-1 drugs are not well-studied, but the press seems to talk about them as if they are—in glowing terms as if their broad adoption is a given and a lifetime attached to the tit of a friendly drug company (with your credit card inserted) is merely a temporary problem. 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.

cm2187 2y ago
How is that different from covid vaccines? The long term risk wasn't known, but covid was super dangerous for a subset of the population, so for those it was absolutely a risk worth taking, and so is obesity.
- DonsDiscountGas 2y ago
  A vaccine only takes a few doses, plus they're pretty cheap. Worst case scenario you get a booster every year. These drugs stop working the second you drop taking them
  - PapaPalpatine 2y ago
    As a former user, “the second you stop taking them” isn’t totally accurate. It does take a few weeks for the effects to wear off and appetite to return.
    - martin_a 2y ago
      I've started using them a few weeks ago, how was your success with them?
      - cm2187 2y ago
        It's down to how much of a diet you do (the drug only manages your appetite). I went hardcore and lost 40kg in 3 months, almost "effortlessly". One meal a day, no sugar, 45min cardio daily. Now trying to figure out where the floor is and planning a progressive reduction in dose/frequency over the next few months. I am lucky I had no side effect and I increased the dosage only sparingly, but people react differently.
        martin_a 2y ago
        Wow, that is crazy and like a 3.500 kcal deficit a day. That's heavy and I'm glad it worked for you! I struggle with cardio, simply don't like it, am more into lifting heavy stuff... :-D What weight did you start out from? 40-50 kg is what I'd like to lose after all, I think.
        cm2187 2y ago
        133kg to 93kg. But I am a big guy, 188cm, so I think my absolute min weight would be 87kg, perhaps a bit more now that I am older. 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.
      - PapaPalpatine 2y ago
        Very successful. I used it as an opportunity to change my lifestyle and eating habits. 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.
  - cm2187 2y ago
    Yeah but you are not meant to do a diet your whole life either, they help you make a diet. If people revert to unhealthy habits after that it is on them. But there is a difference between fasting to lose weight (where you are hungry, very hard to sustain) and a stable diet (where you do not have to fight hunger).
    - ifyoubuildit 2y ago
      You kinda do though. Ideally dieting isn't some activity you do for a little while and then go back to inhaling oreos. Instead you find a long term sustainable lifestyle that doesn't cause you to steadily gain weight.
      - cm2187 2y ago
        I think you are confusing "dieting" and "sustainable lifestyle". Dieting is starving yourself to lose weight. That's not sustainable and those drugs help a lot. But once you are on target weight, you can switch to a sustainable lifestyle where hunger is much less of a problem, just resisting the temptation of the oeros. But that's not hunger, that's gourmandise.
        bryanlarsen 2y ago
        > Dieting is starving yourself to lose weight. No it's not. Diet is just what you eat. It can be healthy or unhealthy.
        ifyoubuildit 2y ago
        I don't think so. Starving yourself is a specific diet. I think of dieting just as being intentional about what you consume.
  - dartharva 2y ago
    > Worst case scenario you get a booster every year. Only a conjecture, since as OP said, the long-term effects haven't been studied for us to be so sure.
    - bryanlarsen 2y ago
      The long-term effects of COVID are pretty darn obvious, though. I know two people with Myalgic Encephalomyelitis from the 2009 flu epidemic and it's nasty. The vaccine was widespread enough that we've got a reasonable upper bound on on the COVID vaccine worst case to make the cost/benefit analysis an easy call.
  - paulkrush 2y ago
    They(you know: those people) need to find a vaccine that does the same thing as these GLP-1s. It seems termination shock is becoming a bigger issue with these new products as time goes on.
  - Spivak 2y ago
    * They're expensive right now because there's a shortage. * 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.
    - cm2187 2y ago
      Though in the UK they cost something like £200 a month, I am saving that in food just by fasting while on those drugs, so it kinds of pays for itself.
      - Spivak 2y ago
        Oh I was considering the $200/mo to be the expensive price. Yeah name brand you can pay $1k/mo but I don't imagine most folks going that route over the generic given the choice. But yeah, that's a good point I suppose. Fewer side effects than meth that's for sure.
- xd1936 2y ago
  Obesity isn't an airborne contagion with an R0 of 5.08 that some percentage of the population was actively denying existence of?
  - grues-dinner 2y ago
    Memetically speaking, it evidently has an R0 above one, though! And I guess there are even such people who deny that there is a "condition" of obesity.
  - cm2187 2y ago
    ...and?
- deleted 2y ago
  [deleted]
- ifyoubuildit 2y ago
  Its not very different from those or any other drugs. There's always a cost benefit analysis. 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"
  - pupppet 2y ago
    They’re not having to turn away people at the hospital because it’s full of obese people.
    - ifyoubuildit 2y ago
      Do you know that for sure? What portion of hospital visits are due to issues downstream of obesity? Heart disease, diabetes, and stroke hospitalize more people than covid ever could have dreamed of.
horsawlarway 2y ago
GLP-1s are relatively well studied, though. At least compared to the vast majority of "new" drugs. 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.
- apothegm 2y ago
  If they’ve been around that long, what changed to make them suddenly so broadly used?
  - zw7 2y ago
    - FDA approval for use for weight loss. Previously this was off-label use - adoption of GLPs into diabetes treatment guidelines
- aaomidi 2y ago
  Also, this effectively eliminating other, well studied and dangerous, health issues definitely makes the risk worth it. 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.
  - slowmovintarget 2y ago
    But diet and exercise are drastically more effective at eliminating these health issues and then some. You can't make a pill for that, though. 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.
ogogmad 2y ago
> The long-term side effects of GLP-1 drugs are not well-studied 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?
hwillis 2y ago
> The long-term side effects of GLP-1 drugs are not well-studied 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.
UI_at_80x24 2y ago
>The long-term side effects of GLP-1 drugs are not well-studied 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.
Log_out_ 2y ago
Lifetime attachments are fantastic .You can not become a offgrid partisan prepper if you are medical dependant on a functioning society . Insulin, hearing aids,the other aids, neural implants, software as a service. To be a stability hostage of society is fantastic .Like Dis or else.

cm2187 2y ago

How is that different from covid vaccines? The long term risk wasn't known, but covid was super dangerous for a subset of the population, so for those it was absolutely a risk worth taking, and so is obesity.

DonsDiscountGas 2y ago
A vaccine only takes a few doses, plus they're pretty cheap. Worst case scenario you get a booster every year. These drugs stop working the second you drop taking them
- PapaPalpatine 2y ago
  As a former user, “the second you stop taking them” isn’t totally accurate. It does take a few weeks for the effects to wear off and appetite to return.
  - martin_a 2y ago
    I've started using them a few weeks ago, how was your success with them?
    - cm2187 2y ago
      It's down to how much of a diet you do (the drug only manages your appetite). I went hardcore and lost 40kg in 3 months, almost "effortlessly". One meal a day, no sugar, 45min cardio daily. Now trying to figure out where the floor is and planning a progressive reduction in dose/frequency over the next few months. I am lucky I had no side effect and I increased the dosage only sparingly, but people react differently.
      - martin_a 2y ago
        Wow, that is crazy and like a 3.500 kcal deficit a day. That's heavy and I'm glad it worked for you! I struggle with cardio, simply don't like it, am more into lifting heavy stuff... :-D What weight did you start out from? 40-50 kg is what I'd like to lose after all, I think.
        cm2187 2y ago
        133kg to 93kg. But I am a big guy, 188cm, so I think my absolute min weight would be 87kg, perhaps a bit more now that I am older. 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.
    - PapaPalpatine 2y ago
      Very successful. I used it as an opportunity to change my lifestyle and eating habits. 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.
- cm2187 2y ago
  Yeah but you are not meant to do a diet your whole life either, they help you make a diet. If people revert to unhealthy habits after that it is on them. But there is a difference between fasting to lose weight (where you are hungry, very hard to sustain) and a stable diet (where you do not have to fight hunger).
  - ifyoubuildit 2y ago
    You kinda do though. Ideally dieting isn't some activity you do for a little while and then go back to inhaling oreos. Instead you find a long term sustainable lifestyle that doesn't cause you to steadily gain weight.
    - cm2187 2y ago
      I think you are confusing "dieting" and "sustainable lifestyle". Dieting is starving yourself to lose weight. That's not sustainable and those drugs help a lot. But once you are on target weight, you can switch to a sustainable lifestyle where hunger is much less of a problem, just resisting the temptation of the oeros. But that's not hunger, that's gourmandise.
      - bryanlarsen 2y ago
        > Dieting is starving yourself to lose weight. No it's not. Diet is just what you eat. It can be healthy or unhealthy.
      - ifyoubuildit 2y ago
        I don't think so. Starving yourself is a specific diet. I think of dieting just as being intentional about what you consume.
- dartharva 2y ago
  > Worst case scenario you get a booster every year. Only a conjecture, since as OP said, the long-term effects haven't been studied for us to be so sure.
  - bryanlarsen 2y ago
    The long-term effects of COVID are pretty darn obvious, though. I know two people with Myalgic Encephalomyelitis from the 2009 flu epidemic and it's nasty. The vaccine was widespread enough that we've got a reasonable upper bound on on the COVID vaccine worst case to make the cost/benefit analysis an easy call.
- paulkrush 2y ago
  They(you know: those people) need to find a vaccine that does the same thing as these GLP-1s. It seems termination shock is becoming a bigger issue with these new products as time goes on.
- Spivak 2y ago
  * They're expensive right now because there's a shortage. * 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.
  - cm2187 2y ago
    Though in the UK they cost something like £200 a month, I am saving that in food just by fasting while on those drugs, so it kinds of pays for itself.
    - Spivak 2y ago
      Oh I was considering the $200/mo to be the expensive price. Yeah name brand you can pay $1k/mo but I don't imagine most folks going that route over the generic given the choice. But yeah, that's a good point I suppose. Fewer side effects than meth that's for sure.
xd1936 2y ago
Obesity isn't an airborne contagion with an R0 of 5.08 that some percentage of the population was actively denying existence of?
- grues-dinner 2y ago
  Memetically speaking, it evidently has an R0 above one, though! And I guess there are even such people who deny that there is a "condition" of obesity.
- cm2187 2y ago
  ...and?
deleted 2y ago
[deleted]
ifyoubuildit 2y ago
Its not very different from those or any other drugs. There's always a cost benefit analysis. 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"
- pupppet 2y ago
  They’re not having to turn away people at the hospital because it’s full of obese people.
  - ifyoubuildit 2y ago
    Do you know that for sure? What portion of hospital visits are due to issues downstream of obesity? Heart disease, diabetes, and stroke hospitalize more people than covid ever could have dreamed of.

horsawlarway 2y ago

GLP-1s are relatively well studied, though. At least compared to the vast majority of "new" drugs. 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.

apothegm 2y ago
If they’ve been around that long, what changed to make them suddenly so broadly used?
- zw7 2y ago
  - FDA approval for use for weight loss. Previously this was off-label use - adoption of GLPs into diabetes treatment guidelines
aaomidi 2y ago
Also, this effectively eliminating other, well studied and dangerous, health issues definitely makes the risk worth it. 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.
- slowmovintarget 2y ago
  But diet and exercise are drastically more effective at eliminating these health issues and then some. You can't make a pill for that, though. 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.

ogogmad 2y ago

> The long-term side effects of GLP-1 drugs are not well-studied 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?

hwillis 2y ago

> The long-term side effects of GLP-1 drugs are not well-studied 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.

UI_at_80x24 2y ago

>The long-term side effects of GLP-1 drugs are not well-studied 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.

Log_out_ 2y ago

Lifetime attachments are fantastic .You can not become a offgrid partisan prepper if you are medical dependant on a functioning society . Insulin, hearing aids,the other aids, neural implants, software as a service. To be a stability hostage of society is fantastic .Like Dis or else.