3 ms·

Do we know what the long-term affects are? Is there any lasting benefit if someone stops taking these types of medication? If one does keep taking it indefinite

Do we know what the long-term affects are? Is there any lasting benefit if someone stops taking these types of medication? If one does keep taking it indefinitely, does the addiction-suppression effect stay the same, or reduces over time?

deleted 2y ago
[deleted]
toomuchtodo 2y ago
There are side effects, but the risk profile is known (is my understanding). It is (at this time) believed to be a forever drug, just like diet and exercise stop working if you stop them. A longer term fix is likely gene therapy (Fractyl Health has a clinical trial in progress, REMAIN-1) vs chronic maintenance. GLP-1s allow us to poke at the human to see what happens. Gene therapy will, hopefully, allow us to implement a permanent fix vs a hotfix (once the risk profile of such a genetic modification is better understood). https://www.remain1study.com/remain-1-study/ https://www.remain1study.com/remain-1-study/
- bossyTeacher 2y ago
  Diet and exercise don't have negative side effects and they are free. Exercise is social too and has lots of side effect benefits beyond the obvious fitness ones
  - toomuchtodo 2y ago
    If no one does them, their risk profile is immaterial. GLP-1s can be manufactured for $5/month. Cheaper than trying to coax the monkey brain into doing things you can't make it do. I cannot speak to the gene therapy cost; balance against lifetime cost of "Western disease" if not provided. Engineer for the way the world is, not the way we wish it was. From your comments, you appear to operate under the belief that people can free will their way to success ("The better option seems to be face the appetite head on rather than putting it on a temporal cage"). That is not what the evidence shows, and I wouldn't ask anyone with a brain chemistry imbalance or dysfunction to attempt to will the condition away when proven interventions are readily and inexpensively available. TLDR We are improving agency in humans using bioengineering, broadly speaking. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight https://www.who.int/news-room/fact-sheets/detail/obesity-and... https://www.cdc.gov/obesity/php/data-research/adult-obesity-facts.html https://www.cdc.gov/obesity/php/data-research/adult-obesity-...
    - bossyTeacher 2y ago
      I find your language usage curious. "trying to coax the monkey brain into doing things you can't make it do", "the way the world is", "people can free will their way to success", "anyone with a brain chemistry imbalance or dysfunction". You seem to imply that people have no self-control and are unable to power through difficulties. Because this is what is all about at the end of the day: self-control, one of the main things that separate us from the rest of the animal kingdom. It is the ability to regulate one's emotions, behaviors, and impulses in the face of temptations and urges. What your parents taught you, your teachers taught you all those years during compulsory education lies on a solid foundation of self-control. Civilisation as we know is built upon it. Depends on it. Yet your language implies that this is not the case. That humans are effectively, like toddlers, unable to use their self regulating powers to reign upon their emotions for the sake of a much better outcome in the long term. Fully unable to choose healthier foods or foods with lower calories. Fully unable to engage in free physical activities such as walking, jogging or running. Truly makes you wonder how civilisations exist at all. The idea that you can improve an individual's agency by having to temporarily disable a part of their brain is nonsensical. Surely, you can temporarily improve a specific decision making outcome (do I eat now?) by doing this. But you are not improving their agency anymore than you can by putting a gun on their head. In both cases, there is an external force temporarily suppressing a part of their normal decision making so they decide not to eat. The underlying problem: lack of self-control is still there. You just tackled a symptom. There are others (deciding not to engage in physical activity for example). A better solution would tackle the lack of self-control rather than some of the symptom. There is already some research on this area and some potential suggestions that if further investigated could help provide a better solution. But unfortunately, the solutions are virtually free and don't involve a lifetime subscription (could very well end up like diabetes medication which is arguably more critical for affected people yet with companies endlessly increasing the patents Disney style) to a drug.
  - JumpCrisscross 2y ago
    > Diet and exercise don't have negative side effects and they are free They're absolutely not free. They fail at a high rate, which incurs medical costs. And when they work, they require--in practice--a lot of follow-up and coaching. It's fairy-tale level mindblowing that we can look at the status quo where nearly half of the industrialised world is obese and get haughty about a drug that medically, demonstrably improves patient outcomes.
    - bossyTeacher 2y ago
      Tell me how much does it cost to do push ups? How much does it cost to do squats? Failing at doing any of these does not incur medical costs. And yes, it takes effort and willpower (like anything worthwile in this life). But none of those cost money. It's fairy-tale level mindblowing that we can look at the status quo where nearly half of the industrialised world is obese and get haughty about a free method (see physical exercise) that medically, demonstrably improves patient outcomes with no negative side effects. That drug is the medical equivalent of a goldberg machine. Exercising your willpower will have more benefits than physical exercise alone: mental health, cardiovascular and strength fitness and you could go on. And it is free. No big farma making money from you
      - lostmsu 2y ago
        It takes time and induces brain fog for at least some time after exercise. There are other side effects too.
        bossyTeacher 2y ago
        > It takes time and induces brain fog for at least some time after exercise Are you serious? How is "taking time" meaning that is not free? And you can't possible use that as a side effect. Brain fog is not even a common side effect. In fact, doing exercise is actually one of the recommended ways to tackle brain fog.
    - HarHarVeryFunny 2y ago
      Obesity is primarily a US problem. It's not the same in Europe, where people walk a lot more, and where portion sizes are normal. A ham and cheese sandwich in the UK would have a slice of ham and of cheese. In the US a deli sandwich is a monstrosity with about 1/4 pound of meat in it.
- HarHarVeryFunny 2y ago
  > just like diet and exercise stop working if you stop them I suppose, but that assumes you are viewing them as temporary weight loss interventions rather than lifestyle. The key is to want to be healthy, and to arrive at a sustainable balance of nutrition and exercise level that works for you to stay at a healthy weight. Fad diets where you are denying yourself pleasures, or going hungry are not sustainable, nor is any extreme exercise regime that you find unpleasant or does not comfortably fit in with your routine.
- stanford_labrat 2y ago
  AFAIK Fractyl's "drug" is not gene therapy but a surgery where they remove part of the lining of your colon. It is not currently possible (nor will it likely be) to use gene therapy for obesity treatments. The technology is not suitable for this kind of medical application. slide 5: https://www.fractyl.com/wp-content/uploads/2024/10/DGVS-2024_German-Registry-Presentation_Fractyl-Health.pdf#new_tab https://www.fractyl.com/wp-content/uploads/2024/10/DGVS-2024...
  - toomuchtodo 2y ago
    Wasn't my understanding from the contact I spoke to at Fractyl and associated docs. Noted to follow up with a domain expert, appreciate the context. Are you available for a paid 30-60 min conversation on the topic? Attempting to fill knowledge gaps, as I am not an expert.
KittenInABox 2y ago
So long as an appropriate level of hormone exists in the body (they're injecting hormones doing this) the effect stays the same. This is like wondering if women need to supplement increasing amounts of estrogen over time (as opposed to supplementing only when needed i.e. birth control or menopause). You can take it indefinitely, but you must take it indefinitely in order for it to keep its effectiveness because the body isn't producing enough of the hormone.
- nkozyra 2y ago
  What people inject is not the hormone itself, but a secretagogue (aside from people who directly inject insulin). > You can take it indefinitely, but you must take it indefinitely in order for it to keep its effectiveness because the body isn't producing enough of the hormone. I don't think we consider this (weight gain due to overeating) to be a GLP-1 deficiency, although I'd be interested to see research on that.
elil17 2y ago
We do know that the benefits stop as soon as you stop taking it. You'll start gaining back weight. No negative long term effects have been observed in humans yet, but some animals in trials were at a higher risk of cancer. We haven't observed any evidence that the addiction-suppression effect reduces over time yet. However, we haven't been studying that effect for very long.
- nkohari 2y ago
  > We do know that the benefits stop as soon as you stop taking it. You'll start gaining back weight. It's more accurate to say that if you're depending on the appetite suppression to eat a sustainable amount of calories, you will begin to gain weight again after stopping the drug. It's possible to use a GLP-1 agonist to lose weight and then keep it off with a proper diet. I took tirzepatide (Mounjaro) for 6 months, lost ~45 lbs., and have not gained any back after stopping the drug in July.
  - HarHarVeryFunny 2y ago
    So what changed for you? Why are you now able to control your calorie intake, but not before (or maybe you could have, but just didn't do it that way)?

deleted 2y ago

[deleted]

toomuchtodo 2y ago

There are side effects, but the risk profile is known (is my understanding). It is (at this time) believed to be a forever drug, just like diet and exercise stop working if you stop them. A longer term fix is likely gene therapy (Fractyl Health has a clinical trial in progress, REMAIN-1) vs chronic maintenance. GLP-1s allow us to poke at the human to see what happens. Gene therapy will, hopefully, allow us to implement a permanent fix vs a hotfix (once the risk profile of such a genetic modification is better understood). https://www.remain1study.com/remain-1-study/ https://www.remain1study.com/remain-1-study/

bossyTeacher 2y ago
Diet and exercise don't have negative side effects and they are free. Exercise is social too and has lots of side effect benefits beyond the obvious fitness ones
- toomuchtodo 2y ago
  If no one does them, their risk profile is immaterial. GLP-1s can be manufactured for $5/month. Cheaper than trying to coax the monkey brain into doing things you can't make it do. I cannot speak to the gene therapy cost; balance against lifetime cost of "Western disease" if not provided. Engineer for the way the world is, not the way we wish it was. From your comments, you appear to operate under the belief that people can free will their way to success ("The better option seems to be face the appetite head on rather than putting it on a temporal cage"). That is not what the evidence shows, and I wouldn't ask anyone with a brain chemistry imbalance or dysfunction to attempt to will the condition away when proven interventions are readily and inexpensively available. TLDR We are improving agency in humans using bioengineering, broadly speaking. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight https://www.who.int/news-room/fact-sheets/detail/obesity-and... https://www.cdc.gov/obesity/php/data-research/adult-obesity-facts.html https://www.cdc.gov/obesity/php/data-research/adult-obesity-...
  - bossyTeacher 2y ago
    I find your language usage curious. "trying to coax the monkey brain into doing things you can't make it do", "the way the world is", "people can free will their way to success", "anyone with a brain chemistry imbalance or dysfunction". You seem to imply that people have no self-control and are unable to power through difficulties. Because this is what is all about at the end of the day: self-control, one of the main things that separate us from the rest of the animal kingdom. It is the ability to regulate one's emotions, behaviors, and impulses in the face of temptations and urges. What your parents taught you, your teachers taught you all those years during compulsory education lies on a solid foundation of self-control. Civilisation as we know is built upon it. Depends on it. Yet your language implies that this is not the case. That humans are effectively, like toddlers, unable to use their self regulating powers to reign upon their emotions for the sake of a much better outcome in the long term. Fully unable to choose healthier foods or foods with lower calories. Fully unable to engage in free physical activities such as walking, jogging or running. Truly makes you wonder how civilisations exist at all. The idea that you can improve an individual's agency by having to temporarily disable a part of their brain is nonsensical. Surely, you can temporarily improve a specific decision making outcome (do I eat now?) by doing this. But you are not improving their agency anymore than you can by putting a gun on their head. In both cases, there is an external force temporarily suppressing a part of their normal decision making so they decide not to eat. The underlying problem: lack of self-control is still there. You just tackled a symptom. There are others (deciding not to engage in physical activity for example). A better solution would tackle the lack of self-control rather than some of the symptom. There is already some research on this area and some potential suggestions that if further investigated could help provide a better solution. But unfortunately, the solutions are virtually free and don't involve a lifetime subscription (could very well end up like diabetes medication which is arguably more critical for affected people yet with companies endlessly increasing the patents Disney style) to a drug.
- JumpCrisscross 2y ago
  > Diet and exercise don't have negative side effects and they are free They're absolutely not free. They fail at a high rate, which incurs medical costs. And when they work, they require--in practice--a lot of follow-up and coaching. It's fairy-tale level mindblowing that we can look at the status quo where nearly half of the industrialised world is obese and get haughty about a drug that medically, demonstrably improves patient outcomes.
  - bossyTeacher 2y ago
    Tell me how much does it cost to do push ups? How much does it cost to do squats? Failing at doing any of these does not incur medical costs. And yes, it takes effort and willpower (like anything worthwile in this life). But none of those cost money. It's fairy-tale level mindblowing that we can look at the status quo where nearly half of the industrialised world is obese and get haughty about a free method (see physical exercise) that medically, demonstrably improves patient outcomes with no negative side effects. That drug is the medical equivalent of a goldberg machine. Exercising your willpower will have more benefits than physical exercise alone: mental health, cardiovascular and strength fitness and you could go on. And it is free. No big farma making money from you
    - lostmsu 2y ago
      It takes time and induces brain fog for at least some time after exercise. There are other side effects too.
      - bossyTeacher 2y ago
        > It takes time and induces brain fog for at least some time after exercise Are you serious? How is "taking time" meaning that is not free? And you can't possible use that as a side effect. Brain fog is not even a common side effect. In fact, doing exercise is actually one of the recommended ways to tackle brain fog.
  - HarHarVeryFunny 2y ago
    Obesity is primarily a US problem. It's not the same in Europe, where people walk a lot more, and where portion sizes are normal. A ham and cheese sandwich in the UK would have a slice of ham and of cheese. In the US a deli sandwich is a monstrosity with about 1/4 pound of meat in it.
HarHarVeryFunny 2y ago
> just like diet and exercise stop working if you stop them I suppose, but that assumes you are viewing them as temporary weight loss interventions rather than lifestyle. The key is to want to be healthy, and to arrive at a sustainable balance of nutrition and exercise level that works for you to stay at a healthy weight. Fad diets where you are denying yourself pleasures, or going hungry are not sustainable, nor is any extreme exercise regime that you find unpleasant or does not comfortably fit in with your routine.
stanford_labrat 2y ago
AFAIK Fractyl's "drug" is not gene therapy but a surgery where they remove part of the lining of your colon. It is not currently possible (nor will it likely be) to use gene therapy for obesity treatments. The technology is not suitable for this kind of medical application. slide 5: https://www.fractyl.com/wp-content/uploads/2024/10/DGVS-2024_German-Registry-Presentation_Fractyl-Health.pdf#new_tab https://www.fractyl.com/wp-content/uploads/2024/10/DGVS-2024...
- toomuchtodo 2y ago
  Wasn't my understanding from the contact I spoke to at Fractyl and associated docs. Noted to follow up with a domain expert, appreciate the context. Are you available for a paid 30-60 min conversation on the topic? Attempting to fill knowledge gaps, as I am not an expert.

KittenInABox 2y ago

So long as an appropriate level of hormone exists in the body (they're injecting hormones doing this) the effect stays the same. This is like wondering if women need to supplement increasing amounts of estrogen over time (as opposed to supplementing only when needed i.e. birth control or menopause). You can take it indefinitely, but you must take it indefinitely in order for it to keep its effectiveness because the body isn't producing enough of the hormone.

nkozyra 2y ago
What people inject is not the hormone itself, but a secretagogue (aside from people who directly inject insulin). > You can take it indefinitely, but you must take it indefinitely in order for it to keep its effectiveness because the body isn't producing enough of the hormone. I don't think we consider this (weight gain due to overeating) to be a GLP-1 deficiency, although I'd be interested to see research on that.

elil17 2y ago

We do know that the benefits stop as soon as you stop taking it. You'll start gaining back weight. No negative long term effects have been observed in humans yet, but some animals in trials were at a higher risk of cancer. We haven't observed any evidence that the addiction-suppression effect reduces over time yet. However, we haven't been studying that effect for very long.

nkohari 2y ago
> We do know that the benefits stop as soon as you stop taking it. You'll start gaining back weight. It's more accurate to say that if you're depending on the appetite suppression to eat a sustainable amount of calories, you will begin to gain weight again after stopping the drug. It's possible to use a GLP-1 agonist to lose weight and then keep it off with a proper diet. I took tirzepatide (Mounjaro) for 6 months, lost ~45 lbs., and have not gained any back after stopping the drug in July.
- HarHarVeryFunny 2y ago
  So what changed for you? Why are you now able to control your calorie intake, but not before (or maybe you could have, but just didn't do it that way)?