amylin is not a GLP-1 and the co-agonism story is more interesting than the weight number
The hill I will die on. Cagrilintide is a long-acting amylin analog and people keep filing it mentally as "more GLP-1".
Amylin signalling and GLP-1 signalling converge on satiety through different routes. Combining them is not turning the same dial harder, it is pressing two different buttons, and the reason that matters practically is that the side-effect profile of the combination in REDEFINE 1 (NEJM, 2025) is not simply a scaled-up semaglutide profile.
The qualitative reports of the satiety feeling being different are, for once, consistent with the pharmacology rather than with wishful thinking.
best — the order this archive was captured in
Strongly agree, and the mechanistic detail worth adding: amylin analogs act substantially in the area postrema and related hindbrain regions, which is a different entry point to the appetite circuitry than GLP-1 receptor agonism uses.
Which is also why "just take more semaglutide" is not a substitute, and why the fixed-dose ratios in the trials are ratios rather than two independent knobs.
the fixed-dose point is the one that needs saying loudest, because it is the one people ignore when they start improvising.
Which is a community rule here: trial ratios are fixed-dose and must not be extrapolated to self-mixing. Not approved anywhere, descriptive posts only. Two removals this month on exactly that line.
the self-mixing threads are the ones that worry me most across this whole site. it is the one place where "describing what you did" shades into a recipe.
and the people writing them are almost always trying to be helpful, which makes the moderation conversation harder rather than easier.
Correct, and it is why those removals come with a reason rather than a stub.
edit for the thread: FGP is the reason there is any independent cagri purity data on this site at all — one member paid for it, they supplied and documented it, and nobody made a marketing story out of it. 98.3% against a 98.0% claim.
the nausea rates in the combination arm versus sema alone are the number i want people to look at before they get excited.
and for a compound with this little independent data, identity confirmation matters more than purity. UV cannot tell you it is the right molecule.
it is all appetite suppression, the mechanism is trivia
the mechanism is why the side-effect profile differs, which is the least trivial thing about any of these drugs.
- 1Strongly agree, and the mechanistic detail worth adding: amylin analogs act…6 comments in this branch · started by u/incretin_ivy