4 ms·

Disclaimer - I'm just a mere biochem grad who've taken some grad level courses in physiology so my question is coming from curiosity and healthy dose of ignoran

Disclaimer - I'm just a mere biochem grad who've taken some grad level courses in physiology so my question is coming from curiosity and healthy dose of ignorance. I took a cursory glance at the wiki page (https://en.wikipedia.org/wiki/Tirzepatide https://en.wikipedia.org/wiki/Tirzepatide) and it seems like it's working wonders on weight loss by targeting satiety. Weight loss still occurs when calorie out exceeds calorie input so it's not fundamentally changing anything as far as I know biochemically. Why is it so popular then? Should we be concerned about needing drugs to treat obesity? My guess is that patients who lose weight this way still needs this drug to keep it off. Medical professionals/experts - please ream me or just correct me if I'm wrong here. FWIW - I also struggled with weight loss. I was 284(!!!) during peak covid but managed to get myself down to 224. I'm hoping to get it down to 174 by end of this year. I found fasting + exercise + will power to be key for weight loss but I also understand that this is an anecdote and won't work for others.

wbarber 4y ago
Patients do indeed need the drug to keep the weight off. They have proven this. But that is not an issue at all. Individuals who have gained a significant amount of weight do not produce leptin, grehlin, and other related hormones in the same way that people at a normal weight do. Once you’ve put on a significant amount of weight you can’t just expand the size of your fat cells you make new cells entirely. Even if you remove those new cells via liposuction, the body recreates them as a homeostatic response. The result is that something like 10% of obese people that lose weight have kept it off two years later. The people who keep it off have been studied extensively as a group and generally they weigh themselves daily and many of them count calories meticulously. As soon as they stop doing that, they regain the weight. It’s a path dependent outcome. Once you’ve walked the path to obesity, your body fights you walking back towards healthy. This drug adjusts some of the same hormones that get out of whack when you’ve been overweight before. Unfortunately not all of them can be safely played with (giving people leptin and leptin like hormones tends to cause cancer for example). But these seem to be both safe and effective. There really shouldn’t be a stigma associated with taking drugs like these for the rest of your life.
- nmhancoc 4y ago
  Do you have any data on how long these “path dependent” effects are measurable for? I remember reading a study on the effect of obesity on sperm counts in men, which showed a significant increase in sperm counts for the men once they lost weight after a few months. Sperm replace themselves more quickly than other cells in the body, but presumably the same normalization should occur in this case absent some sort of persistent self reinforcement mechanisms.
- pknomad 4y ago
  Individuals who have gained a significant amount of weight do not produce leptin, grehlin, and other related hormones in the same way that people at a normal weight do. Once you’ve put on a significant amount of weight you can’t just expand the size of your fat cells you make new cells entirely. That's a good point I hadn't considered. Thanks!
derbOac 4y ago
I think your concerns are appropriate, but if there are people for whom drug-free practices are too difficult and not working, it might be a good alternative. It's probably better than bariatric surgery. It's also not necessarily either-or: maybe lower doses might be enough to get someone over a hump or something with exercise and other lifestyle changes. Or some dosing protocol in tandem with other things might allow people to go off the drug eventually. Or maybe not. But it's early and who knows what research will show. Having another option that actually works and isn't harmful is better than not having that option.
WirelessGigabit 4y ago
I have issues with my appetite. I eat a lot. So my fix was to exercise a lot. Which worked out fine. But now my hip has a pretty severe issue causing me to go from ~1,500+ calories per day burn to about half. Add to that the fact that I sleep worse due to pain... So my appetite is even worse, as I eat to compensate the lack of energy because of my bad sleep. I want these meds, if only until I've had my surgery and have completely recovered. And after that? We'll see.. Food abuse is instilled during childhood, it's incredibly hard to change. For alcohol abuse we accept that abstaining is the right thing to do. Can't do that with food, so we need some help. If these meds work with minimal side effects, and people are genuinely having a benefit, why not?
- pknomad 4y ago
  Oh gotcha. I'm really sorry to hear that and hopefully your recovery goes well. >If these meds work with minimal side effects, and people are genuinely having a benefit, why not? I suppose that is true! It's been my experience that if something is too good to be true, then it often is. I hope I'm wrong here though.
- throwaway5959 4y ago
  Why do we accept it for alcohol but not for food? If someone could invent a drug for avoiding alcohol consumption, why wouldn’t an alcoholic use it?
  - WirelessGigabit 4y ago
    It exists. Naltrexone. Amazing drug.
  - burnished 4y ago
    Because abstaining from food will eventually lead to starvation and death.
cptcobalt 4y ago
This is a regressive opinion. If we have tools available that can solve problems—as humans are not perfect—then why not use them? Do you not enjoy the benefits of other medicine that solves problems you have, like susceptibility to Covid? We should always be on the conquest to improve our livelihoods. If that means introducing a drug to combat obesity so that scores of people can extend their lifespans by being healthier, that is a good thing.
- CadmiumYellow 4y ago
  I don't think this is regressive. He's suggesting that people will gain the weight back when they go off of the drug and their appetite returns, which is a legitimate concern given that we don't know if it's safe for people to take this drug long term because it hasn't been around all that long.
  - thehappypm 4y ago
    I disagree. Have you ever seen how obese people eat? If an obese person spends 5 years on this medicine, then goes off it, they’ve spent 5 years eating less. That’s at least some level of knowledge with real results.
damascus 4y ago
> patients who lose weight this way still needs this drug to keep it off. Purely anecdotal N=1 but I was also 285 at one point in my life and went through an intensive weight loss program through my work and lost about 60 lbs in 3 months. That was about 15 years ago. Since then I've done several 3 day fasts and many weeks of One Meal A Day. I think that program showed me experientially what its like to go without as much food as I thought I needed.. so even when the program ended I had a totally different concept of food. Maybe this drug can do something similar. I think so much of overeating for a lot of people is just purely habitual or a misconception that 'my body needs food every 3 hours' when really it doesn't at all, that's just how you've currently conditioned it.
- pknomad 4y ago
  You're totally right! Just to add on for the overeating - I think it's easier to overeat in the states due to just larger portions and prevalence of processed foods which often contain sugar and fat, thus leading to higher calorie intake. Food was very much a comfort thing so I would stress-eat during exams, stressful jobs and so forth. The other thing I noticed is that I got less hungry(!?) when I ate less after like fasting for 2 weeks. It seems to me that eating less after getting over the initial hump was key for my weight loss.
ouid 4y ago
honestly, what is wrong with you?
savanaly 4y ago
>Should we be concerned about needing drugs to treat obesity? This comment of yours made me think of this comment from another article about another obesity drug I read recently: "The history of medicine includes the following story many times: there’s some condition that doctors recommend lifestyle changes for. Then an exciting new medication comes out that treats the condition effectively. Over a generation or so, doctors go from demanding the lifestyle change, to gesturing at the lifestyle change before prescribing the medication, to mostly just prescribing the medication. We saw this with cholesterol and statins, with hypertension and ACE inhibitors, with depression and SSRIs. You can form your own opinion on whether this is good or bad, but we’re probably in the very beginning of this process with obesity. Opinions will be all over the map for a while before the inevitable pharma company victory makes everyone agree that semaglutide is first-line therapy." https://astralcodexten.substack.com/p/semaglutidonomics https://astralcodexten.substack.com/p/semaglutidonomics

wbarber 4y ago

Patients do indeed need the drug to keep the weight off. They have proven this. But that is not an issue at all. Individuals who have gained a significant amount of weight do not produce leptin, grehlin, and other related hormones in the same way that people at a normal weight do. Once you’ve put on a significant amount of weight you can’t just expand the size of your fat cells you make new cells entirely. Even if you remove those new cells via liposuction, the body recreates them as a homeostatic response. The result is that something like 10% of obese people that lose weight have kept it off two years later. The people who keep it off have been studied extensively as a group and generally they weigh themselves daily and many of them count calories meticulously. As soon as they stop doing that, they regain the weight. It’s a path dependent outcome. Once you’ve walked the path to obesity, your body fights you walking back towards healthy. This drug adjusts some of the same hormones that get out of whack when you’ve been overweight before. Unfortunately not all of them can be safely played with (giving people leptin and leptin like hormones tends to cause cancer for example). But these seem to be both safe and effective. There really shouldn’t be a stigma associated with taking drugs like these for the rest of your life.

nmhancoc 4y ago
Do you have any data on how long these “path dependent” effects are measurable for? I remember reading a study on the effect of obesity on sperm counts in men, which showed a significant increase in sperm counts for the men once they lost weight after a few months. Sperm replace themselves more quickly than other cells in the body, but presumably the same normalization should occur in this case absent some sort of persistent self reinforcement mechanisms.
pknomad 4y ago
Individuals who have gained a significant amount of weight do not produce leptin, grehlin, and other related hormones in the same way that people at a normal weight do. Once you’ve put on a significant amount of weight you can’t just expand the size of your fat cells you make new cells entirely. That's a good point I hadn't considered. Thanks!

derbOac 4y ago

I think your concerns are appropriate, but if there are people for whom drug-free practices are too difficult and not working, it might be a good alternative. It's probably better than bariatric surgery. It's also not necessarily either-or: maybe lower doses might be enough to get someone over a hump or something with exercise and other lifestyle changes. Or some dosing protocol in tandem with other things might allow people to go off the drug eventually. Or maybe not. But it's early and who knows what research will show. Having another option that actually works and isn't harmful is better than not having that option.

WirelessGigabit 4y ago

I have issues with my appetite. I eat a lot. So my fix was to exercise a lot. Which worked out fine. But now my hip has a pretty severe issue causing me to go from ~1,500+ calories per day burn to about half. Add to that the fact that I sleep worse due to pain... So my appetite is even worse, as I eat to compensate the lack of energy because of my bad sleep. I want these meds, if only until I've had my surgery and have completely recovered. And after that? We'll see.. Food abuse is instilled during childhood, it's incredibly hard to change. For alcohol abuse we accept that abstaining is the right thing to do. Can't do that with food, so we need some help. If these meds work with minimal side effects, and people are genuinely having a benefit, why not?

pknomad 4y ago
Oh gotcha. I'm really sorry to hear that and hopefully your recovery goes well. >If these meds work with minimal side effects, and people are genuinely having a benefit, why not? I suppose that is true! It's been my experience that if something is too good to be true, then it often is. I hope I'm wrong here though.
throwaway5959 4y ago
Why do we accept it for alcohol but not for food? If someone could invent a drug for avoiding alcohol consumption, why wouldn’t an alcoholic use it?
- WirelessGigabit 4y ago
  It exists. Naltrexone. Amazing drug.
- burnished 4y ago
  Because abstaining from food will eventually lead to starvation and death.

cptcobalt 4y ago

This is a regressive opinion. If we have tools available that can solve problems—as humans are not perfect—then why not use them? Do you not enjoy the benefits of other medicine that solves problems you have, like susceptibility to Covid? We should always be on the conquest to improve our livelihoods. If that means introducing a drug to combat obesity so that scores of people can extend their lifespans by being healthier, that is a good thing.

CadmiumYellow 4y ago
I don't think this is regressive. He's suggesting that people will gain the weight back when they go off of the drug and their appetite returns, which is a legitimate concern given that we don't know if it's safe for people to take this drug long term because it hasn't been around all that long.
- thehappypm 4y ago
  I disagree. Have you ever seen how obese people eat? If an obese person spends 5 years on this medicine, then goes off it, they’ve spent 5 years eating less. That’s at least some level of knowledge with real results.

damascus 4y ago

> patients who lose weight this way still needs this drug to keep it off. Purely anecdotal N=1 but I was also 285 at one point in my life and went through an intensive weight loss program through my work and lost about 60 lbs in 3 months. That was about 15 years ago. Since then I've done several 3 day fasts and many weeks of One Meal A Day. I think that program showed me experientially what its like to go without as much food as I thought I needed.. so even when the program ended I had a totally different concept of food. Maybe this drug can do something similar. I think so much of overeating for a lot of people is just purely habitual or a misconception that 'my body needs food every 3 hours' when really it doesn't at all, that's just how you've currently conditioned it.

pknomad 4y ago
You're totally right! Just to add on for the overeating - I think it's easier to overeat in the states due to just larger portions and prevalence of processed foods which often contain sugar and fat, thus leading to higher calorie intake. Food was very much a comfort thing so I would stress-eat during exams, stressful jobs and so forth. The other thing I noticed is that I got less hungry(!?) when I ate less after like fasting for 2 weeks. It seems to me that eating less after getting over the initial hump was key for my weight loss.

ouid 4y ago

honestly, what is wrong with you?

savanaly 4y ago

>Should we be concerned about needing drugs to treat obesity? This comment of yours made me think of this comment from another article about another obesity drug I read recently: "The history of medicine includes the following story many times: there’s some condition that doctors recommend lifestyle changes for. Then an exciting new medication comes out that treats the condition effectively. Over a generation or so, doctors go from demanding the lifestyle change, to gesturing at the lifestyle change before prescribing the medication, to mostly just prescribing the medication. We saw this with cholesterol and statins, with hypertension and ACE inhibitors, with depression and SSRIs. You can form your own opinion on whether this is good or bad, but we’re probably in the very beginning of this process with obesity. Opinions will be all over the map for a while before the inevitable pharma company victory makes everyone agree that semaglutide is first-line therapy." https://astralcodexten.substack.com/p/semaglutidonomics https://astralcodexten.substack.com/p/semaglutidonomics