It’s an interesting question, think the ARPA-H phase 3 trial for longevity will be including another pill GLP-A, so that might provide valuable data
I’m personally still concerned around if GLP-A increases insulin and/or changes the insulin cycle that could be bad for longevity.
Interestingly to the discussion about about muscle, the very reason I worry about insulin up = growth up might actually help with muscle gain/retention from resistance training. So it might be that someone doing resistance training on GLP-As gains more muscle than someone doing CR alone at the same calorie deficit?
One other way pill based GLP-As with not too long half life’s might be interesting is they can help doing say 3-5-7 day complete fasts? Not sure about the ramp up and down mechanics, but if people could do complete fasts easier than it it to do Prolon, and hence did it 4-6 times a year or something might be a good addition to longevity protocols
@AlexKChen what are your latest thoughts on GLP-As in longevity, recall you thinking a lot about this before and trying out different things
@A_User re myostatin inhibition, would probably want to avoid ones that also inhibit GDF11. Below still is a proof of concept despite that
The phase 2 BELIEVE trial showed that the addition of bimagrumab, an activin type II receptor-targeted antibody that promotes muscle hypertrophy, could preserve the weight reduction seen with the glucagon-like peptide-1 receptor agonist (GLP-1 RA), semaglutide, while also improving body composition, preserving lean muscle mass, and boosting physical function in adults living with obesity without concomitant diabetes.
One could also add back GDF11:
https://www.nature.com/articles/s41598-021-81669-8
See
Administration of recombinant mature GDF11 (0.01 mg/kg bodyweight, three times, intraperitoneal) significantly suppressed the reduction of muscle strength
And Fig 3C