Been chewing on this one for a while because the “tirz works better bc GIP” framing gets pulled into every sema vs tirz thread and the comparison design is doing more work than people realize. The SURMOUNT and STEP data isn’t comparing matched doses. Tirz at 15mg achieves greater weight loss than sema at 2.4mg, full stop. So when someone says “at comparable weight loss the side effect profile is X” or “the lean mass preservation is Y,” they’re comparing mismatched doses of two different receptor occupancy profiles. The GIP contribution can’t be cleanly isolated from that design. My own n=1, for what it’s worth: 18 months on tirz, A1c 8.4 down to 5.6, CGM 14-day average from 148 to 102 between weeks 4 and 12. I haven’t been on sema so I can’t speak to the head-to-head directly. What I can say is the postprandial flattening on CGM was steeper and earlier than my A1c shift, which is the kind of signal a standard fasting glucose + A1c comparison between the two compounds would smooth right over. The colonic transit piece is where I think the GIP story gets oversold further. Upper GI motility data exists for both, but the “GIP causes constipation” framing isn’t supported cleanly bc stool water content and colonic fermentation are more likely downstream of bile acid and microbiome shifts than direct GIP activity at the colon. Anyone seen a tirz vs sema comparison that actually held GLP-1 receptor occupancy constant? I went looking and came up mostly empty.
edit: clarifying