6 ms·

How does it work? Does it reduce the calorie intake by decreasing the appetite? Your body burns more calories because the drug sets the thermostat higher?! Or s

How does it work? Does it reduce the calorie intake by decreasing the appetite? Your body burns more calories because the drug sets the thermostat higher?! Or something else? I don't know how to feel about the idea that we need treatment for being overweight in general.

toomuchtodo 2y ago
It patches a reward center in your brain, reducing appetite, but also patching addiction reward center activity. https://recursiveadaptation.com/p/the-growing-scientific-case-for-using https://recursiveadaptation.com/p/the-growing-scientific-cas... > The consistency that I'm hearing from all across patient groups is gain of control, whereas previously, there was a loss of control… All of a sudden they're able to step back and say, 'oh, well I had this shopping phenomenon that was going on, gambling, addiction, or alcoholism, and all of a sudden, it just stopped,' - Dr. Gitanjali Srivastava, Vanderbilt Medical Center
- HarHarVeryFunny 2y ago
  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.
  - 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)?
- unshavedyak 2y ago
  Sidenote, my SO recently started a generic GLP-1 shot. It has far more side effects, at least during ramp up - than just reward center. Notably a wide array of food either make them sick to their stomach or have colon related issues (diarrhea or constipation). I suspect i do observe reward changes as well, but especially in the first few weeks it felt like i was observing weight loss strictly because they struggled to eat so much food without getting sick. So many of the foods they still wanted would just make them sick immediately or hours later. I think they read that much of this is temporary to the ramp-up time, though. So hopefully in ~6 months they'll be on the full dose and won't have so many nausea/diarrhea issues.
  - JumpCrisscross 2y ago
    > many of the foods they still wanted would just make them sick immediately or hours later Can you name some of the foods? Never been on GLP-1 drugs. But a good amount of fast food leaves me feeling lethargic and, if I eat it too quickly, nauseated afterwards.
    - unshavedyak 2y ago
      Their doctor suggested that they would drop a lot of weight fast, and they wanted to make sure they focused on eating lots of protein. So that's one restriction, medically prescribed meal types. On top of that, fatty meals, larger meals, and iirc fast carb heavy meals would all cause either nausea or diarrhea. Interestingly their mother is on the identical same generic GLP-1 shot, and has mostly the same side effects. It's kinda difficult to enumerate all the foods that went poorly, and it doesn't always feel logical. We eat a lot (entirely?) home cooked meals, so it's not like i'm even talking fast food here. Off the top of my head a lot of dark green vegs have been working well. Brassicas and the like. I should note that they're still quite happy on the drug. They still eat normally enough that it's not like they're only eating broccoli or something. We just have to plan meals very purposefully. It's also a lot of trial and error to find the subset that works.
      - petesergeant 2y ago
- bossyTeacher 2y ago
  Sounds worrying to me as it means this is essentially a lifetime drug. As soon as you stop taking it, your appetite returns and so does your old weight. The better option seems to be face the appetite head on rather than putting it on a temporal cage
  - nkohari 2y ago
    > Sounds worrying to me as it means this is essentially a lifetime drug. As soon as you stop taking it, your appetite returns and so does your old weight. I see this said all the time about GLP-1 agonists, and it's a mischaracterization. It is true that when you stop taking the drug, your appetite is no longer suppressed, but you can still keep the weight off by eating a sustainable amount of calories. Usually, the biggest challenge with weight loss is sticking with it, since it's normally miserable and takes a very long time. Taking a GLP-1 agonist speeds the process and makes it much more tolerable. I lost ~45 lbs. (~205 to ~160) in 6 months by taking tirzepatide (Mounjaro), and if I had done it without the drug it would have taken at least twice as long and been much more difficult.
    - bossyTeacher 2y ago
      > you can still keep the weight off by eating a sustainable amount of calories. This was always true and we know this is not the reason why people are overweight
      - nkohari 2y ago
        It's true that the solution is more complicated than "just eat fewer calories", but it's also true that some people just need their baseline to be reset. I'm perfectly capable of maintaining my weight at ~160 lbs, but losing a large amount of weight to get there was difficult enough that I didn't try. A friend did pretty much everything to lose weight after she had children but couldn't, went on GLP-1 agonist for a few months, lost it all and kept it off since. People always lament that, like most drugs, the effects of a GLP-1 agonist stop when you stop taking it. What I'm saying is it doesn't necessarily matter. Some people will need continued support, some won't. Taking the drug isn't a "life sentence" and you aren't guaranteed to re-gain the weight after you stop.
- petesergeant 2y ago
  > It patches a reward center in your brain Notably it also slows digestion though, so you feel full earlier and for longer.
swsieber 2y ago
The way I've heard it put is that it "quiets the food noise"
hbosch 2y ago
Tirzepatide (aka Zepbound/Mounjaro) is called a dual-action GLP-1/GIP agonist. The GLP-1 action overall makes you feel less hungry, basically. The GIP action slows gastric emptying (how quickly food moves from your stomach to your small intenstine) so you feel full longer. It also has a modest effect on lipolysis, which means it does help somewhat in breaking down adipose tissue (fat) to use for energy more efficiently. Semaglutide is a GLP-1 agonist only. Retratutide is a newer drug that is triple-action. Generally on these drugs the action does not induce more "calorie burning", they are used mostly to modulate caloric intake. >I don't know how to feel about the idea that we need treatment for being overweight in general. Obesity is by orders of magnitude the worst public health issue facing humanity. Obesity makes every disease worse. Obese people are more likely to develop cancer, cardiovascular issues, respiratory issues, dementia, diabetes, and other afflictions. Obesity often leads to depression, lack of motivation, lower libidos, overall worse moods in general. Of course there are "levels" to it, it's not to say everyone has to be a bodybuilder to be happy and healthy. Of course not. This is not about being slightly overweight, or "wanting to lose 15 lbs for summer"... But in almost every way, being fat makes life worse for the majority of people.

toomuchtodo 2y ago

It patches a reward center in your brain, reducing appetite, but also patching addiction reward center activity. https://recursiveadaptation.com/p/the-growing-scientific-case-for-using https://recursiveadaptation.com/p/the-growing-scientific-cas... > The consistency that I'm hearing from all across patient groups is gain of control, whereas previously, there was a loss of control… All of a sudden they're able to step back and say, 'oh, well I had this shopping phenomenon that was going on, gambling, addiction, or alcoholism, and all of a sudden, it just stopped,' - Dr. Gitanjali Srivastava, Vanderbilt Medical Center

HarHarVeryFunny 2y ago
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.
- 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)?
unshavedyak 2y ago
Sidenote, my SO recently started a generic GLP-1 shot. It has far more side effects, at least during ramp up - than just reward center. Notably a wide array of food either make them sick to their stomach or have colon related issues (diarrhea or constipation). I suspect i do observe reward changes as well, but especially in the first few weeks it felt like i was observing weight loss strictly because they struggled to eat so much food without getting sick. So many of the foods they still wanted would just make them sick immediately or hours later. I think they read that much of this is temporary to the ramp-up time, though. So hopefully in ~6 months they'll be on the full dose and won't have so many nausea/diarrhea issues.
- JumpCrisscross 2y ago
  > many of the foods they still wanted would just make them sick immediately or hours later Can you name some of the foods? Never been on GLP-1 drugs. But a good amount of fast food leaves me feeling lethargic and, if I eat it too quickly, nauseated afterwards.
  - unshavedyak 2y ago
    Their doctor suggested that they would drop a lot of weight fast, and they wanted to make sure they focused on eating lots of protein. So that's one restriction, medically prescribed meal types. On top of that, fatty meals, larger meals, and iirc fast carb heavy meals would all cause either nausea or diarrhea. Interestingly their mother is on the identical same generic GLP-1 shot, and has mostly the same side effects. It's kinda difficult to enumerate all the foods that went poorly, and it doesn't always feel logical. We eat a lot (entirely?) home cooked meals, so it's not like i'm even talking fast food here. Off the top of my head a lot of dark green vegs have been working well. Brassicas and the like. I should note that they're still quite happy on the drug. They still eat normally enough that it's not like they're only eating broccoli or something. We just have to plan meals very purposefully. It's also a lot of trial and error to find the subset that works.
    - petesergeant 2y ago
bossyTeacher 2y ago
Sounds worrying to me as it means this is essentially a lifetime drug. As soon as you stop taking it, your appetite returns and so does your old weight. The better option seems to be face the appetite head on rather than putting it on a temporal cage
- nkohari 2y ago
  > Sounds worrying to me as it means this is essentially a lifetime drug. As soon as you stop taking it, your appetite returns and so does your old weight. I see this said all the time about GLP-1 agonists, and it's a mischaracterization. It is true that when you stop taking the drug, your appetite is no longer suppressed, but you can still keep the weight off by eating a sustainable amount of calories. Usually, the biggest challenge with weight loss is sticking with it, since it's normally miserable and takes a very long time. Taking a GLP-1 agonist speeds the process and makes it much more tolerable. I lost ~45 lbs. (~205 to ~160) in 6 months by taking tirzepatide (Mounjaro), and if I had done it without the drug it would have taken at least twice as long and been much more difficult.
  - bossyTeacher 2y ago
    > you can still keep the weight off by eating a sustainable amount of calories. This was always true and we know this is not the reason why people are overweight
    - nkohari 2y ago
      It's true that the solution is more complicated than "just eat fewer calories", but it's also true that some people just need their baseline to be reset. I'm perfectly capable of maintaining my weight at ~160 lbs, but losing a large amount of weight to get there was difficult enough that I didn't try. A friend did pretty much everything to lose weight after she had children but couldn't, went on GLP-1 agonist for a few months, lost it all and kept it off since. People always lament that, like most drugs, the effects of a GLP-1 agonist stop when you stop taking it. What I'm saying is it doesn't necessarily matter. Some people will need continued support, some won't. Taking the drug isn't a "life sentence" and you aren't guaranteed to re-gain the weight after you stop.
petesergeant 2y ago
> It patches a reward center in your brain Notably it also slows digestion though, so you feel full earlier and for longer.

swsieber 2y ago

The way I've heard it put is that it "quiets the food noise"

hbosch 2y ago

Tirzepatide (aka Zepbound/Mounjaro) is called a dual-action GLP-1/GIP agonist. The GLP-1 action overall makes you feel less hungry, basically. The GIP action slows gastric emptying (how quickly food moves from your stomach to your small intenstine) so you feel full longer. It also has a modest effect on lipolysis, which means it does help somewhat in breaking down adipose tissue (fat) to use for energy more efficiently. Semaglutide is a GLP-1 agonist only. Retratutide is a newer drug that is triple-action. Generally on these drugs the action does not induce more "calorie burning", they are used mostly to modulate caloric intake. >I don't know how to feel about the idea that we need treatment for being overweight in general. Obesity is by orders of magnitude the worst public health issue facing humanity. Obesity makes every disease worse. Obese people are more likely to develop cancer, cardiovascular issues, respiratory issues, dementia, diabetes, and other afflictions. Obesity often leads to depression, lack of motivation, lower libidos, overall worse moods in general. Of course there are "levels" to it, it's not to say everyone has to be a bodybuilder to be happy and healthy. Of course not. This is not about being slightly overweight, or "wanting to lose 15 lbs for summer"... But in almost every way, being fat makes life worse for the majority of people.