does incretin actually matter or is it forum lore at this point
The title is the whole question — does incretin actually matter or is it forum lore at this point — but here is why I am asking. Went looking for human data on a mechanism everybody here asserts. Found preclinical work and one small study. That was clarifying. Tried to build a mental model from mechanism alone and…
Does the effect persist with continued dosing or does tolerance develop?
Does the effect persist with continued dosing or does tolerance develop?
Adding the caveat the paper itself makes in its limitations section, which is stronger than anything in this thread.
Is that from a human study or a preclinical model?
Yes. The discussion section is where the authors say what they actually think, and almost nobody here reads it.
Tolerance to the gastric effect develops with continued exposure while the appetite effect largely persists. That single fact explains most of the "it settles but it still works" pattern the side-effect board reports.
Was completely wrong about the gastric emptying story in a thread here two years ago. Someone corrected me with a citation and I have not made that mistake since.
Correcting my own comment: I attributed that to the GIP arm and the paper attributes it to the GLP-1 arm.
GLP-1 receptor agonism acts both peripherally — insulin secretion in a glucose-dependent way, slowed gastric emptying — and centrally, on appetite regulation. The central component is the better explanation for sustained intake reduction.
Agreed that receptor distribution is the key to the side-effect map. It is not a mystery, it is anatomy.
Asked a question here that I thought was stupid and got three papers back. Best thread I have been in on this site.
Is there any human data on that mechanism yet?
a mechanism you can state is not a mechanism you have demonstrated
Retitled to distinguish preclinical from clinical, which the original ran together.