5 ms·

What’s the downside to this magical drug. There has to be a downside…

by dyauspitr 4mo ago

ceejayoz 4mo ago
Why does there have to be a downside? What was the downside of washing hands before surgery?
- 9x39 4mo ago
  Because our bodies are delicate systems of networks, and inputs in one area can have complex/unpredictable outputs elsewhere, it seems. Typically, if something "works", there often appear to be side effects. A free lunch is rare. https://www.uclahealth.org/news/article/understanding-medication-side-effects-and-homeostasis https://www.uclahealth.org/news/article/understanding-medica...
  - krackers 4mo ago
    The fact that GLP-1 seems to have roles not just in satiety but that agonists seem to reduce other types of impulsiveness (e.g. gambling, shopping) is interesting. That's not something you'd predict as a consequence, and perhaps is downstream of some gut-brain connection. Of course we already manipulate brain chemistry in other more direct ways with antidepressants so perhaps any unwanted second-order effects could be minor in comparison to the profile of existing antidepressants .
    - 9x39 4mo ago
      Yeah, that's a good point. I hadn't heard about impulsiveness. I had read that taste preferences changed - e.g., salty, sweet, savory, fatty: https://pmc.ncbi.nlm.nih.gov/articles/PMC7105351/ https://pmc.ncbi.nlm.nih.gov/articles/PMC7105351/ I've been watching developments on how GLP1s seem to go beyond just hunger/insulin response, even how they may affect symptoms of polycystic ovarian syndrome (PCOS), which is difficult on women who have it: https://academic.oup.com/ejendo/article/194/3/S25/8488941 https://academic.oup.com/ejendo/article/194/3/S25/8488941
  - JumpCrisscross 4mo ago
    > Typically, if something "works", there often appear to be side effects Unless it’s literally a deficit. There isn’t a downside to treating vitamin C deficiency with vitamin C.
- OscarCunningham 4mo ago
  One argument would be that Ozempic doesn't give your body any additional resources. It just triggers your body to behave in a different way. But if the changes it causes are universally good, why didn't evolution already make your body work that way? I suppose the counterargument would be that modern life is different from the evolutionary environment, and so it's possible for a change to be beneficial now that wasn't beneficial then. But it would still be good to understand better the mechanism of the effect of Ozempic on things like addiction.
  - ceejayoz 4mo ago
    > But if the changes it causes are universally good, why didn't evolution already make your body work that way? That’s not how evolution works.
  - crooked-v 4mo ago
    > But if the changes it causes are universally good, why didn't evolution already make your body work that way? We evolved in an environment where every bit of food took hours of effort and food preservation was impossible, so the only logical thing to do with extra food was feast and store up as much fat as possible for lean times. We're still many generations away from evolving to compensate for the discovery of fire, let alone everything that came after that.
  - microgpt 4mo ago
    There are people with more or less sensitive GLP-1 receptors today, who have lesser or greater impulsivity. If some event occurs where only those with lower impulsivity survive, then the future population will have more sensitive GLP-1 receptors. This is the only way that happen - noticeable evolution is always driven by population bottlenecks or strong selective pressure. In the absence of those, mutation just keeps expanding the gene pool so more different candidates are available for the next bottleneck. In case an event happens where only red-haired people survive, good thing some are available, otherwise there's no reason to think everyone will have red hair in the future.
kolinko 4mo ago
And downsides of penicilin? There are some but they are massively offset by not having alt consequences
- subtlejellyfish 4mo ago
  Penicillin resistant bacteria?
- culi 4mo ago
  There are massive downsides to any antibiotic. A single dose of a broad-spectrum antibiotic can permanently alter a kid's gut microbiome and make them more likely to develop a variety of mental health issues like depression https://theconversation.com/how-childhood-infections-requiring-antibiotics-may-increase-risks-of-mental-illness-110965 https://theconversation.com/how-childhood-infections-requiri... https://www.scientificamerican.com/article/a-single-course-of-antibiotics-may-reshape-the-gut-microbiome-for-years/ https://www.scientificamerican.com/article/a-single-course-o...
- sevenseacat 4mo ago
  As someone with a severe allergy, lots of downsides to me!
Aaargh20318 4mo ago
The downside is that they make you eat less thereby taking away one of the few things that make life worth living.
- SubiculumCode 4mo ago
  That is the silliest take ever. I am on GLP-1s, and I still enjoy my food..maybe more than ever before.
- microgpt 4mo ago
  You should get in touch with a therapist to help you find meaning in life that isn't just eating food. Or get a girlfriend - i heard that helps most people.
  - Aaargh20318 4mo ago
    Ah yes, a therapist. One of those people who will try to gaslight you into thinking spending 40 hours a week in dayprison is a meaningful life.
    - qsxfthnkp2322 4mo ago
      So tell me more ;)
    - microgpt 4mo ago
      What do you do with the other 128 hours?
      - Aaargh20318 4mo ago
        Sit in front of the TV like a zombie because I’m too tired to do anything else.
        microgpt 4mo ago
        So that's the problem. Might you suffer from anhedonia, a common part of depression? It can also be ADHD-related. ADHD is a common co-diagnosis of autism which is a common co-diagnosis of using HN, and ADHD basically means your reward system is messed up on all axes, not just the ones that cause AD and H. I'm not diagnosing you, just throwing out words you might possibly look up.
cflewis 4mo ago
Nothing in this world is free, GLP-1s have their downsides (excluding cost). Mostly it's nausea and gastrointestinal distress side effects. These tend to cool down over time, but it'll put a ceiling on how big a dose you can tolerate. Some people can't tolerate a dose at any level.
pandaman 4mo ago
Even if there are zero effects other than the advertised weight reduction, one downside is obvious from the comments here - some people will stop exercising. While exercise has many positive effects, which I'd argue are more important than the weight loss, the latter is the primary reason many people exercise and likely to stop when given the weight loss by other means.
- subtlejellyfish 4mo ago
  We should stop telling people that exercise is a primary driver of weight loss. That said, exercise has a direct impact on metabolic health which is pretty necessary to maintain a healthy weight.
- chrisco255 4mo ago
  Most people are achieving weight loss by dietary changes. It takes a massive amount of exercise to significantly alter your calorie balance. Definitely good for you either way but most people who exercise also want to be toned or muscular.
  - pandaman 4mo ago
    Define "massive". People do successfully and reliably get in shape through exercise. Aerobic exercise that gets HR up for an hour or more will significantly alter your calorie balance. I agree that more people don't go through exercise rote though.
    - padjo 4mo ago
      An hour of fairly vigorous cardio every day will give you what, 3-400 kcals of extra calories to play around? Something you can easily overcome by eating a donut, which you will absolutely crave after that hour and feel you deserve. Exercise is absolutely useless for weight loss if it isn't coupled with a controlled diet.
      - pandaman 4mo ago
tayo42 4mo ago
Don't they age your face pretty badly?
- sevenseacat 4mo ago
  Not by themselves - its the result of weight loss that can make your skin sag a bit.
declan_roberts 4mo ago
Some downsides: 1. They make you stop eating, which for most of human history kills you. 2. They are a life-long treatment and kind of expensive unless you go gray market. 3. Gastrointestinal issues especially when titrating up.
- chrisco255 4mo ago
  1. They don't make you stop altogether, they just make you feel full on less calories, which is good when you are in a calorie dense environment like modern society. 2. Not necessary here either if dietary habits are permanently altered, which can happen more easily after several months on GLPs. 3. Perhaps!
weregiraffe 4mo ago
What's the downside to antibiotics?
- dyauspitr 4mo ago
  Gut biome destruction that has some far reaching effects including mental ones.
cagenut 4mo ago
the downside is it allows us to continue to avoid solving the real problem ideologues will tell you this is that all mankind suddenly lost their ability to exert self-discipline a few decades ago science points to a broad combination of things like corn syrup and seed oils simply making food too addictivly-rewarding and calorie rich for our nervous and endocrine systems to handle. so, do we reform the farm bill and fast food industries, or do we take the antidote?
- microgpt 4mo ago
  No one is steering the ship. You have the same right to try to fuck over Pepsi (which owns like half of all addictive food brands) by taking GLP1RAs as they do to try to fuck you over by putting who knows what in their food. Some of that stuff they put in food is probably designed to antagonize your GLP-1 receptors, you know. They didn't know what those were, but they did know when they put it in food, you bought more! *cough* Pringles
- mathgladiator 4mo ago
  Solving the underlying problem has been amazing. I wish more people could do it. I have given up helping others since my solution was to embrace a carnivore lifestyle. But then im just in a tribal cult with amazing health.
danny_codes 4mo ago
Long-term downsides tend not to show up in studies for many years. For example, these drugs might increase cancer rates, but we wouldn't know for a few decades. I imagine though that on-balance they'll be net positive because being overweight is just so bad for you.

What’s the downside to this magical drug. There has to be a downside…

ceejayoz 4mo ago

Why does there have to be a downside? What was the downside of washing hands before surgery?

9x39 4mo ago
Because our bodies are delicate systems of networks, and inputs in one area can have complex/unpredictable outputs elsewhere, it seems. Typically, if something "works", there often appear to be side effects. A free lunch is rare. https://www.uclahealth.org/news/article/understanding-medication-side-effects-and-homeostasis https://www.uclahealth.org/news/article/understanding-medica...
- krackers 4mo ago
  The fact that GLP-1 seems to have roles not just in satiety but that agonists seem to reduce other types of impulsiveness (e.g. gambling, shopping) is interesting. That's not something you'd predict as a consequence, and perhaps is downstream of some gut-brain connection. Of course we already manipulate brain chemistry in other more direct ways with antidepressants so perhaps any unwanted second-order effects could be minor in comparison to the profile of existing antidepressants .
  - 9x39 4mo ago
    Yeah, that's a good point. I hadn't heard about impulsiveness. I had read that taste preferences changed - e.g., salty, sweet, savory, fatty: https://pmc.ncbi.nlm.nih.gov/articles/PMC7105351/ https://pmc.ncbi.nlm.nih.gov/articles/PMC7105351/ I've been watching developments on how GLP1s seem to go beyond just hunger/insulin response, even how they may affect symptoms of polycystic ovarian syndrome (PCOS), which is difficult on women who have it: https://academic.oup.com/ejendo/article/194/3/S25/8488941 https://academic.oup.com/ejendo/article/194/3/S25/8488941
- JumpCrisscross 4mo ago
  > Typically, if something "works", there often appear to be side effects Unless it’s literally a deficit. There isn’t a downside to treating vitamin C deficiency with vitamin C.
OscarCunningham 4mo ago
One argument would be that Ozempic doesn't give your body any additional resources. It just triggers your body to behave in a different way. But if the changes it causes are universally good, why didn't evolution already make your body work that way? I suppose the counterargument would be that modern life is different from the evolutionary environment, and so it's possible for a change to be beneficial now that wasn't beneficial then. But it would still be good to understand better the mechanism of the effect of Ozempic on things like addiction.
- ceejayoz 4mo ago
  > But if the changes it causes are universally good, why didn't evolution already make your body work that way? That’s not how evolution works.
- crooked-v 4mo ago
  > But if the changes it causes are universally good, why didn't evolution already make your body work that way? We evolved in an environment where every bit of food took hours of effort and food preservation was impossible, so the only logical thing to do with extra food was feast and store up as much fat as possible for lean times. We're still many generations away from evolving to compensate for the discovery of fire, let alone everything that came after that.
- microgpt 4mo ago
  There are people with more or less sensitive GLP-1 receptors today, who have lesser or greater impulsivity. If some event occurs where only those with lower impulsivity survive, then the future population will have more sensitive GLP-1 receptors. This is the only way that happen - noticeable evolution is always driven by population bottlenecks or strong selective pressure. In the absence of those, mutation just keeps expanding the gene pool so more different candidates are available for the next bottleneck. In case an event happens where only red-haired people survive, good thing some are available, otherwise there's no reason to think everyone will have red hair in the future.

kolinko 4mo ago

And downsides of penicilin? There are some but they are massively offset by not having alt consequences

subtlejellyfish 4mo ago
Penicillin resistant bacteria?
culi 4mo ago
There are massive downsides to any antibiotic. A single dose of a broad-spectrum antibiotic can permanently alter a kid's gut microbiome and make them more likely to develop a variety of mental health issues like depression https://theconversation.com/how-childhood-infections-requiring-antibiotics-may-increase-risks-of-mental-illness-110965 https://theconversation.com/how-childhood-infections-requiri... https://www.scientificamerican.com/article/a-single-course-of-antibiotics-may-reshape-the-gut-microbiome-for-years/ https://www.scientificamerican.com/article/a-single-course-o...
sevenseacat 4mo ago
As someone with a severe allergy, lots of downsides to me!

Aaargh20318 4mo ago

The downside is that they make you eat less thereby taking away one of the few things that make life worth living.

SubiculumCode 4mo ago
That is the silliest take ever. I am on GLP-1s, and I still enjoy my food..maybe more than ever before.
microgpt 4mo ago
You should get in touch with a therapist to help you find meaning in life that isn't just eating food. Or get a girlfriend - i heard that helps most people.
- Aaargh20318 4mo ago
  Ah yes, a therapist. One of those people who will try to gaslight you into thinking spending 40 hours a week in dayprison is a meaningful life.
  - qsxfthnkp2322 4mo ago
    So tell me more ;)
  - microgpt 4mo ago
    What do you do with the other 128 hours?
    - Aaargh20318 4mo ago
      Sit in front of the TV like a zombie because I’m too tired to do anything else.
      - microgpt 4mo ago
        So that's the problem. Might you suffer from anhedonia, a common part of depression? It can also be ADHD-related. ADHD is a common co-diagnosis of autism which is a common co-diagnosis of using HN, and ADHD basically means your reward system is messed up on all axes, not just the ones that cause AD and H. I'm not diagnosing you, just throwing out words you might possibly look up.

cflewis 4mo ago

Nothing in this world is free, GLP-1s have their downsides (excluding cost). Mostly it's nausea and gastrointestinal distress side effects. These tend to cool down over time, but it'll put a ceiling on how big a dose you can tolerate. Some people can't tolerate a dose at any level.

pandaman 4mo ago

Even if there are zero effects other than the advertised weight reduction, one downside is obvious from the comments here - some people will stop exercising. While exercise has many positive effects, which I'd argue are more important than the weight loss, the latter is the primary reason many people exercise and likely to stop when given the weight loss by other means.

subtlejellyfish 4mo ago
We should stop telling people that exercise is a primary driver of weight loss. That said, exercise has a direct impact on metabolic health which is pretty necessary to maintain a healthy weight.
chrisco255 4mo ago
Most people are achieving weight loss by dietary changes. It takes a massive amount of exercise to significantly alter your calorie balance. Definitely good for you either way but most people who exercise also want to be toned or muscular.
- pandaman 4mo ago
  Define "massive". People do successfully and reliably get in shape through exercise. Aerobic exercise that gets HR up for an hour or more will significantly alter your calorie balance. I agree that more people don't go through exercise rote though.
  - padjo 4mo ago
    An hour of fairly vigorous cardio every day will give you what, 3-400 kcals of extra calories to play around? Something you can easily overcome by eating a donut, which you will absolutely crave after that hour and feel you deserve. Exercise is absolutely useless for weight loss if it isn't coupled with a controlled diet.
    - pandaman 4mo ago

tayo42 4mo ago

Don't they age your face pretty badly?

sevenseacat 4mo ago
Not by themselves - its the result of weight loss that can make your skin sag a bit.

declan_roberts 4mo ago

Some downsides: 1. They make you stop eating, which for most of human history kills you. 2. They are a life-long treatment and kind of expensive unless you go gray market. 3. Gastrointestinal issues especially when titrating up.

chrisco255 4mo ago
1. They don't make you stop altogether, they just make you feel full on less calories, which is good when you are in a calorie dense environment like modern society. 2. Not necessary here either if dietary habits are permanently altered, which can happen more easily after several months on GLPs. 3. Perhaps!

weregiraffe 4mo ago

What's the downside to antibiotics?

dyauspitr 4mo ago
Gut biome destruction that has some far reaching effects including mental ones.

cagenut 4mo ago

the downside is it allows us to continue to avoid solving the real problem ideologues will tell you this is that all mankind suddenly lost their ability to exert self-discipline a few decades ago science points to a broad combination of things like corn syrup and seed oils simply making food too addictivly-rewarding and calorie rich for our nervous and endocrine systems to handle. so, do we reform the farm bill and fast food industries, or do we take the antidote?

microgpt 4mo ago
No one is steering the ship. You have the same right to try to fuck over Pepsi (which owns like half of all addictive food brands) by taking GLP1RAs as they do to try to fuck you over by putting who knows what in their food. Some of that stuff they put in food is probably designed to antagonize your GLP-1 receptors, you know. They didn't know what those were, but they did know when they put it in food, you bought more! *cough* Pringles
mathgladiator 4mo ago
Solving the underlying problem has been amazing. I wish more people could do it. I have given up helping others since my solution was to embrace a carnivore lifestyle. But then im just in a tribal cult with amazing health.

danny_codes 4mo ago

Long-term downsides tend not to show up in studies for many years. For example, these drugs might increase cancer rates, but we wouldn't know for a few decades. I imagine though that on-balance they'll be net positive because being overweight is just so bad for you.