[Discussion] the mechanism advice in here is 3 years out of date
the mechanism advice in here is 3 years out of date. It is the sort of thing everyone half-believes and nobody writes down. The relevant figures are 3 years, and they come from the same log I have kept the whole time. Spent an evening on the receptor distribution literature and the side-effect map suddenly stopped…
Cosigning on GIP. The genuinely interesting thing is that the biology is not settled and the clinical result is nonetheless robust.
Started reading limitations sections first. It has changed how much weight I give to almost everything posted here.
Correction: that is glucose-dependent insulin secretion, which is why hypoglycaemia risk is low as monotherapy. Not the same claim as you made.
the central appetite effect is doing more work than the gut effect
Are we talking about receptor affinity or clinical potency?
Went looking for human data on a mechanism everybody here asserts. Found preclinical work and one small study. That was clarifying.
Agreed that receptor distribution is the key to the side-effect map. It is not a mystery, it is anatomy.
Agreed — the incretin effect is the load-bearing concept and everything downstream reads differently once you have it.
Tried to build a mental model from mechanism alone and produced a confident prediction that the trial data flatly contradicted.