i can confirm that the “rebound effect” when you get off it is crazy. IIRC, for type two diabetics there was a pretty substantial reduction in all-cause mortality when on it (iirc 10% relative risk reduction?), so at least for that use case it’s a pretty great intervention. for people who are already skinny though I’m less convinced by it.
Also, someone I know who tried it got insane lethargy but no appetite suppression and gained weight. (they were only on it for two weeks though.) She was sleeping for about 14 hours a day. This was on a 3mg every other day dose, taken orally.
I think it probably is now. I haven't done a deep lit review & really only have cursory knowledge, but it is widely regarded as by far and away the most effective weight loss intervention (avg. loss is like 60-80% 'excess' bf and like 40-60% total body weight long-term). My understanding is that the main issues are a very limited diet post-op (your stomach is reduced by 90% so you eat like 8 meals throughout the day and many struggle to get 100g protein/day), loose skin after weight loss, strict eligibility criteria (40+ bmi, tried other treatments, etc.) and cost (though it's only like 15-25k for bariatric surgery out of pocket, which is like 1.5 years of out of pocket Wegovy cost at present; my mom was paying like $1200/month before switching to Tirzepatide). I don't think it's all that invasive anymore either b/c most are done laparoscopically. IMO the GLP-1s fill a gap for the marginal 30-40 bmi people who aren't categorically morbidly obese (though bmi is a crude measure obv), but even the 30-40 people would've been considered laughably fat not 50 years ago; more of them would probably have better outcomes if they seriously considered the surgery and found a way to get it done. To me it seems like a self-protective narrative to them ("I'm fat but I'm not *that* fat to cut my stomach in half") or fear of surgery, or some combination thereof.
Will likely write on this in the future, but metformin is much preferable to glp-1s in treatment of type 2 diabetes due to insulin sensitizing effects. Re longevity, it’s a decent geroprotector/senolytic but less preferable to rapamycin imo. There are also some serious concerns around birth defects from paternal use: “The diabetes drug metformin is associated with higher rates of genital birth defects among boys when taken by fathers during the three-month window prior to conception, according to a study funded by NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)”.
Berberine has a very similar MOA if you’re looking for a low-grade metformin-like OTC compound.
i can confirm that the “rebound effect” when you get off it is crazy. IIRC, for type two diabetics there was a pretty substantial reduction in all-cause mortality when on it (iirc 10% relative risk reduction?), so at least for that use case it’s a pretty great intervention. for people who are already skinny though I’m less convinced by it.
Also, someone I know who tried it got insane lethargy but no appetite suppression and gained weight. (they were only on it for two weeks though.) She was sleeping for about 14 hours a day. This was on a 3mg every other day dose, taken orally.
Great post! Here's one thing I've wondered from all the discussion of GLP-1 agonists: Is the gastric bypass underrated?
I think it probably is now. I haven't done a deep lit review & really only have cursory knowledge, but it is widely regarded as by far and away the most effective weight loss intervention (avg. loss is like 60-80% 'excess' bf and like 40-60% total body weight long-term). My understanding is that the main issues are a very limited diet post-op (your stomach is reduced by 90% so you eat like 8 meals throughout the day and many struggle to get 100g protein/day), loose skin after weight loss, strict eligibility criteria (40+ bmi, tried other treatments, etc.) and cost (though it's only like 15-25k for bariatric surgery out of pocket, which is like 1.5 years of out of pocket Wegovy cost at present; my mom was paying like $1200/month before switching to Tirzepatide). I don't think it's all that invasive anymore either b/c most are done laparoscopically. IMO the GLP-1s fill a gap for the marginal 30-40 bmi people who aren't categorically morbidly obese (though bmi is a crude measure obv), but even the 30-40 people would've been considered laughably fat not 50 years ago; more of them would probably have better outcomes if they seriously considered the surgery and found a way to get it done. To me it seems like a self-protective narrative to them ("I'm fat but I'm not *that* fat to cut my stomach in half") or fear of surgery, or some combination thereof.
curious what your thoughts on metformin are given it being hailed as a life-extension/weight loss hero for non-diabetics and many use it long term
Will likely write on this in the future, but metformin is much preferable to glp-1s in treatment of type 2 diabetes due to insulin sensitizing effects. Re longevity, it’s a decent geroprotector/senolytic but less preferable to rapamycin imo. There are also some serious concerns around birth defects from paternal use: “The diabetes drug metformin is associated with higher rates of genital birth defects among boys when taken by fathers during the three-month window prior to conception, according to a study funded by NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)”.
Berberine has a very similar MOA if you’re looking for a low-grade metformin-like OTC compound.