unpopular opinion: most of what gets said here about gastric emptying is guesswork
unpopular opinion: most of what gets said here about gastric emptying is guesswork. Making the case below, and I expect to lose some of it in the comments.
Spent an evening on the receptor distribution literature and the side-effect map suddenly stopped looking random.
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.
Receptor expression in a tissue is necessary but not sufficient for an effect. You also need the agonist to reach it at relevant exposure, and that is where a lot of confident mechanism talk falls down.
Corrections welcome, especially the pedantic ones. Pedantry is how this board earns its reputation.
best — the order this archive was captured in
Left up and flaired Explainer. This is the standard of post the board was created for.
half-life is why these are weekly and not daily
Tolerance to the gastric effect develops with continued exposure while the appetite effect largely persists. That single fact explains most of the "it settles but it still works" pattern 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.
Cosigning on GIP.
This is the concept everything else on this board is downstream of.
Asked a question here that I thought was stupid and got three papers back. Best thread I have been in on this site.
Correction: that is glucose-dependent insulin secretion, which is why hypoglycaemia risk is low as monotherapy. Not the same claim as you made.
That study was in a rodent model. Worth stating, since the thread has been reading it as human data.
preclinical is not clinical and rodents are not small people
Small fix — it slows gastric emptying, it does not halt it, and the distinction matters for the mechanism you are proposing.
Correcting my own comment: I attributed that to the GIP arm and the paper attributes it to the GLP-1 arm.
receptor agonism is not the same as receptor activation in every tissue
receptor agonism is not the same as receptor activation in every tissue
kian_balogun is right that mechanism gives direction and not magnitude. Worth pinning.
GIP is the arm people argue about because the biology is genuinely unsettled
- 1Tolerance to the gastric effect develops with continued exposure while the…12 comments in this branch · started by u/aa_analysis_andy