[Meta] proposal — a flair for incretin posts
proposal — a flair for incretin posts. This affects how posts get sorted and removed, so it belongs in the open.
Started reading limitations sections first. It has changed how much weight I give to almost everything posted here.
The half-life explanation was the thing that made weekly dosing intuitive for me rather than arbitrary.
Tried to build a mental model from mechanism alone and produced a confident prediction that the trial data flatly contradicted.
That is everything I have. The rest is opinion and I have tried to keep it out.
best — the order this archive was captured in
The incretin effect is the observation that oral glucose provokes a larger insulin response than intravenous glucose at matched glycaemia, and the difference is mediated by gut hormones. That is the foundation the whole class sits on.
Is that from a human study or a preclinical model?
Went looking for human data on a mechanism everybody here asserts. Found preclinical work and one small study. That was clarifying.
Push back: a receptor being expressed in a tissue does not tell you the agonist reaches it at therapeutic exposure.
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.