[Discussion] we are measuring mechanism at the wrong time and calling it noise
we are measuring mechanism at the wrong time and calling it noise, and I am aware this is a minority view on this board. Glucose-dependent insulin secretion is why hypoglycaemia risk is low as monotherapy: the effect scales with glycaemia rather than acting unconditionally. Tolerance to the gastric effect develops…
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.
Cosigning on GIP. The genuinely interesting thing is that the biology is not settled and the clinical result is nonetheless robust.
Same view. Tolerance developing to the gastric effect while the appetite effect persists explains most of what 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.
Spent an evening on the receptor distribution literature and the side-effect map suddenly stopped looking random.
GIP is the arm people argue about because the biology is genuinely unsettled
receptor distribution is why the side effects are where they are
GIP is the arm people argue about because the biology is genuinely unsettled
aa_analysis_andy is right that mechanism gives direction and not magnitude. Worth pinning.