receptor is the most under-discussed thing on this board
Posting this as a discussion rather than a claim: receptor is the most under-discussed thing on this board. 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…
Push back: a receptor being expressed in a tissue does not tell you the agonist reaches it at therapeutic exposure.
Push back: a receptor being expressed in a tissue does not tell you the agonist reaches it at therapeutic exposure.
formulary_fighter is right that mechanism gives direction and not magnitude. Worth pinning.
formulary_fighter is right that mechanism gives direction and not magnitude.
This is the concept everything else on this board is downstream of.
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.
This. Albumin binding and modification are why the half-life is what it is, and it is a design decision rather than an accident.
Yes. The central component is the one that explains the reports on this site better than gastric emptying does.
a mechanism you can state is not a mechanism you have demonstrated
tolerance to the gastric effect develops, appetite effect largely persists
Agreed that receptor distribution is the key to the side-effect map. It is not a mystery, it is anatomy.
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.
preclinical is not clinical and rodents are not small people
the central appetite effect is doing more work than the gut effect