CagriSema combo beats sema and cagrilintide alone, but the real test is GI tolerance
Posted by rachel_ketogen in Research & News - 2 points, 4 comments.
Novo's once-weekly CagriSema data is out and the combo dropped A1c more than either drug on its own, with weight loss numbers that actually look competitive with tirzepatide in some subgroups. That part isnt surprising, stacking an amylin analog with a GLP-1 hits appetite and gastric emptying from two angles so of course it works better on paper.
What I want to see is the side effect profile at the higher doses, because cagrilintide alone already makes people pretty nauseous and adding semaglutide on top is a lot of gut slowing. The efficacy numbers are cool but if 30% of people drop out because they cant eat without wanting to die then the real world numbers are gonna look very different.
For anyone tracking their own numbers, how are you weighing efficacy vs tolerability when you look at these combo trials?
Comments
- weekendnate: Yeah the GI ceiling is exactly what kills most of these in practice. Tirzepatide worked fine for me until it didn't, and the dose where the scale finally moved was also the dose where I lived on saltines and ginger chews for two weeks. Efficacy on paper means nothing if compliance craters at month four. The dropout rate in the trial is the number I'd watch, not the mean A1c drop. Surrogate endpoints always look great until you look at discontinuation. Cagrilintide alone at higher doses already
- grinder265: Yeah same, tirz hit a wall for me around the higher titration steps and the nausea never really settled, just became background radiation i learned to ignore lol. The dropout number is what i wanna see, not the headline efficacy. Surrogate endpoints always look great til you check who actually finished the trial.
- rachel_ketogen: The background radiation thing is way too real, thats basically what happened to a few people in the early tirz trials too, they just stopped reporting it after a certain point. I track my own GI symptoms in a spreadsheet like a nerd and the nausea-then-normalize pattern is real but it varies wildly person to person. My gut (pun intended) is that these combo trials are gonna have tighter dropout windows than the original sema trials just because of that stacking effect on the gut. The 30% I thre
- rachel_ketogen: Yeah that saltines and ginger chews stretch sounds miserable, sorry you went through that. And youre right about surrogate endpoints, the mean is doing a lot of work when 30% of the cohort bounced. The week eight bailing point is exactly what im worried about too, thats right when most people titrate up and the gut catches up. Im watching the per-protocol vs mITT gap more than the headline number, if its huge that tells you the average person didnt actually tolerate the dose that produced the r
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