[Paper] amylin co-agonism is genuinely different pharmacology, not just more GLP-1
amylin co-agonism is genuinely different pharmacology, not just more GLP-1. I have gone back and forth on this for months.
The mental model, in four steps, that makes the rest of this site legible.
One: gut hormones amplify the insulin response to food. Two: agonists at those receptors act peripherally on insulin secretion and gastric emptying, and centrally on appetite. Three: structural modification gives them a long half-life, so exposure is smooth and weekly. Four: tolerance develops to some effects and not to others.
From those four, most of what the experience boards report falls out: why the side effects cluster early, why they settle at a stable dose, why appetite reduction persists, and why the scale and the appetite move on different clocks.
Went looking for human data on a mechanism everybody here asserts. Found preclinical work and one small study. That was clarifying.
Started reading limitations sections first. It has changed how much weight I give to almost everything posted here.
I will update this if the picture changes rather than quietly leaving it up.
best — the order this archive was captured in
GLP-1 receptor agonism acts both peripherally — insulin secretion in a glucose-dependent way, slowed gastric emptying — and centrally, on appetite regulation. The central component is the better explanation for sustained intake reduction.
What was the exposure in that experiment relative to therapeutic?
What was the exposure in that experiment relative to therapeutic?
Adding the caveat the paper itself makes in its limitations section, which is stronger than anything in this thread.
That study was in a rodent model. Worth stating, since the thread has been reading it as human data.
Yes. The central component is the one that explains the reports on this site better than gastric emptying does.
preclinical is not clinical and rodents are not small people
gastric emptying slows, it does not stop
preclinical is not clinical and rodents are not small people
This is the concept everything else on this board is downstream of.
The half-life explanation was the thing that made weekly dosing intuitive for me rather than arbitrary.
the central appetite effect is doing more work than the gut effect
Asked a question here that I thought was stupid and got three papers back. Best thread I have been in on this site.
a mechanism you can state is not a mechanism you have demonstrated
a mechanism you can state is not a mechanism you have demonstrated
Disagreeing with this specific inference — that is a preclinical result being read as human pharmacology.
Spent an evening on the receptor distribution literature and the side-effect map suddenly stopped looking random.
incretin effect first, then everything else in this board makes sense
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.
half-life is why these are weekly and not daily
- 1GLP-1 receptor agonism acts both peripherally — insulin secretion in a…11 comments in this branch · started by u/nadia_bakker