three years of receptor threads, summarised so you do not have to read them
Thinking out loud about this: three years of receptor threads, summarised so you do not have to read them. GIP receptor biology is genuinely unsettled — there is a live argument about agonism versus antagonism at the receptor — and the clinical results are robust regardless, which is an uncomfortable and interesting…
glucagon agonism sounds paradoxical until you read the energy expenditure work
Cosigning on GIP. The genuinely interesting thing is that the biology is not settled and the clinical result is nonetheless robust.
incretin effect first, then everything else in this board makes sense
Correction: that is glucose-dependent insulin secretion, which is why hypoglycaemia risk is low as monotherapy. Not the same claim as you made.
Tried to build a mental model from mechanism alone and produced a confident prediction that the trial data flatly contradicted.
That conflates receptor affinity with clinical potency. They are related and they are not the same thing.
Does the effect persist with continued dosing or does tolerance develop?
The half-life explanation was the thing that made weekly dosing intuitive for me rather than arbitrary.
Cosigning on GIP.
This is the concept everything else on this board is downstream of.
Small fix — it slows gastric emptying, it does not halt it, and the distinction matters for the mechanism you are proposing.