[Discussion] the mechanism advice in here is 3 years out of date
the mechanism advice in here is 3 years out of date.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 looking random.
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.
Research-use-only material is not approved for human use and nothing here should be read as a recommendation to use it.
best — the order this archive was captured in
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 position.
Small fix — it slows gastric emptying, it does not halt it, and the distinction matters for the mechanism you are proposing.
Small fix — it slows gastric emptying, it does not halt it, and the distinction matters for the mechanism you are proposing.
Agreed — and it is why the central and peripheral stories are complementary rather than rival.
Right — mechanism gives you a direction. It never gives you an effect size and people use it as though it does.
That conflates receptor affinity with clinical potency. They are related and they are not the same thing.
mechanism explains a direction, not a magnitude
What was the exposure in that experiment relative to therapeutic?
Asked a question here that I thought was stupid and got three papers back. Best thread I have been in on this site.
read the discussion section, that is where the honesty lives
The half-life explanation was the thing that made weekly dosing intuitive for me rather than arbitrary.
Yes. The discussion section is where the authors say what they actually think, and almost nobody here reads it.
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.
Same view. Tolerance developing to the gastric effect while the appetite effect persists explains most of what the side-effect board reports.
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.
- 1Cosigning on GIP. The genuinely interesting thing is that the biology is not…9 comments in this branch · started by u/camila_mensa