[Discussion] incretin is doing more work than we give it credit for
incretin is doing more work than we give it credit for — a position I have arrived at slowly and would like tested. 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…
receptor agonism is not the same as receptor activation in every tissue
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.
Same view. Tolerance developing to the gastric effect while the appetite effect persists explains most of what the side-effect board reports.
Do you have the paper, or a summary of it?
receptor distribution is why the side effects are where they are
Long half-life in this class comes from structural modification that promotes albumin binding and resists enzymatic degradation. Weekly dosing is a consequence of the molecule, not a convenience decision.
Which receptor arm are you attributing that to?
Which receptor arm are you attributing that to?
Adding the caveat the paper itself makes in its limitations section, which is stronger than anything in this thread.
Does the effect persist with continued dosing or does tolerance develop?
Is there any human data on that mechanism yet?
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.
Correcting my own comment: I attributed that to the GIP arm and the paper attributes it to the GLP-1 arm.