the n=1 stack posts attributing BP normalization to reta are interesting but they have an attribution problem that I keep coming back to. the phase 2 data (Jastreboff et al., NEJM 2023) showed meaningful cardiometabolic improvements alongside the weight loss. but the trial wasn’t designed to isolate the GCG receptor’s contribution to BP from the weight loss contribution. lose 28 lbs at any age and systolic usually drops 5-15 points on its own. that’s well-documented and boring. what’s less boring: the glucagon receptor has known natriuretic and vasodilatory properties independent of weight. there’s a plausible direct pathway where GCG agonism increases renal sodium excretion and reduces vascular resistance. the question is whether reta’s BP improvement exceeds what weight loss alone predicts, and the phase 2 data doesn’t cleanly answer that because there’s no weight-matched control arm. the DSIP layer makes attribution even harder. sleep quality is a real BP moderator - nocturnal BP dipping is heavily tied to sympathetic tone, which poor sleep disrupts. if DSIP is actually improving sleep architecture (small studies suggest it might shift SWS), you’ve got two plausible mechanisms running simultaneously and no way to separate them. I went looking for any head-to-head comparing reta vs. sema/tirz on BP per kg lost. came up mostly empty. that comparison would tell you a lot about whether the GCG component is earning its keep here. anyone seen data on that, or is this still purely inferential?