seven months on tirzepatide, down 41, been tracking everything. got curious abt mTOR inhibitors bc of some aging research threads and now wondering if that’s what GLP-1s actually do. the three-trial pattern (cardiomyopathy, CFS, ovarian aging) all pointing at the same mTOR problem seems like it could be the whole underlying mechanism, or maybe it’s a completely separate pathway i’m mixing up. does tirz directly affect mTOR or are those two different things entirely? trying to understand what’s actually happening with the drug.
one piece worth adding to the mTOR thread that doesn’t usually come up: there’s some literature on GLP-1 receptor signaling intersecting with AMPK activation in hepatocytes and beta cells, and AMPK is upstream of mTORC1 inhibition. so the directionally accurate version is probably “GLP-1s likely modulate mTOR indirectly via AMPK and improved insulin sensitivity,” not “GLP-1s are mTOR inhibitors.” rapamycin is a direct mTORC1 inhibitor, that’s a categorically different claim. the other piece I’d add is that a lot of what looks like an mTOR-flavored benefit on tirz (autophagy markers, reduced ectopic fat, mitochondrial function moving) is hard to disentangle from straight-up caloric restriction and weight loss.
CR alone moves mTOR signaling in basically every model organism we have, and 41 lbs down in seven months is a very large CR signal on its own. so the question of “is tirz hitting mTOR mechanistically” is partially a question of “is there anything left after you subtract the CR effect,” and afaik nobody’s cleanly isolated that in humans. i log fasting insulin and trig:HDL alongside weight on the dark mode charts in careclinic, the chart colors don’t strain at 11pm which is when I usually look at trends. fwiw the insulin number is the one that’s tracked the tirz timeline most cleanly for me, more than weight has.
The fasting insulin’s the real metric, weight’s just noise in these early months. You could be making progress and you just won’t see it on the scale.
“fasting insulin’s the real metric, weight’s just noise” is half right and half doing too much work. fasting insulin is absolutely the better signal for what’s actually changing metabolically, agreed, but calling weight “noise” overcorrects. the two aren’t measuring the same thing, weight is a downstream composite (fluid, glycogen, fat, lean mass) and fasting insulin is a snapshot of where the pancreas is sitting that morning, and a single draw varies enough that i wouldn’t call it the metric either, i’d call it one of several. ime two fasting insulin draws a few weeks apart on the same protocol can come back meaningfully different with nothing else changed, so treating any single value as the truth and the scale as noise gets the hierarchy wrong. trig:HDL and fasting glucose belong in that same bucket too.