[Paper] receptor distribution and why the GI effects were predictable
receptor distribution and why the GI effects were predictable. Change my mind, genuinely — I have no stake in being right about this.
Tried to build a mental model from mechanism alone and produced a confident prediction that the trial data flatly contradicted.
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.
That is everything I have. The rest is opinion and I have tried to keep it out.
best — the order this archive was captured in
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.
The half-life explanation was the thing that made weekly dosing intuitive for me rather than arbitrary.
The half-life explanation was the thing that made weekly dosing intuitive for me rather than arbitrary.
sig_figs_sam is right that mechanism gives direction and not magnitude. Worth pinning.
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.
Asked a question here that I thought was stupid and got three papers back. Best thread I have been in on this site.
Does the effect persist with continued dosing or does tolerance develop?
Retitled to distinguish preclinical from clinical, which the original ran together.
the peripheral and central stories are not in competition
Read the primary paper after arguing about the summary for a fortnight. The discussion section said almost the opposite of what the thread had concluded.
Correction: that is glucose-dependent insulin secretion, which is why hypoglycaemia risk is low as monotherapy. Not the same claim as you made.
Retitled to distinguish preclinical from clinical, which the original ran together.
Agreed — and it is why the central and peripheral stories are complementary rather than rival.
Started reading limitations sections first. It has changed how much weight I give to almost everything posted here.
Same view. Tolerance developing to the gastric effect while the appetite effect persists explains most of what the side-effect board reports.
Citations welcome and expected here — this is the one board where "source?" is a compliment.
I would not read that in vitro number across to a person. The conditions are nothing like physiological.
Are we talking about receptor affinity or clinical potency?
- 1Retitled to distinguish preclinical from clinical, which the original ran…7 comments in this branch · started by u/incretin_ivy