someone explain appetite to me like I have not read a paper in years
someone explain appetite to me like I have not read a paper in years, and I want the answer with the reasoning attached rather than just the conclusion.
Glucose-dependent insulin secretion is why hypoglycaemia risk is low as monotherapy: the effect scales with glycaemia rather than acting unconditionally.
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.
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.
Please do not ask me what dose you should be on. I genuinely do not know and neither does anyone else here.
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.
Tried to build a mental model from mechanism alone and produced a confident prediction that the trial data flatly contradicted.
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Do you have the paper, or a summary of it?
Yes. The central component is the one that explains the reports on this site better than gastric emptying does.
Push back: a receptor being expressed in a tissue does not tell you the agonist reaches it at therapeutic exposure.
Cosigning on GIP. The genuinely interesting thing is that the biology is not settled and the clinical result is nonetheless robust.
Careful — you have a plausible mechanism and no evidence that it is the operative one in the case you are describing.
Which receptor arm are you attributing that to?
gastric emptying slows, it does not stop
Is there any human data on that mechanism yet?
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.
a mechanism you can state is not a mechanism you have demonstrated
the central appetite effect is doing more work than the gut effect
Agreed — the incretin effect is the load-bearing concept and everything downstream reads differently once you have it.
This. Albumin binding and modification are why the half-life is what it is, and it is a design decision rather than an accident.
dose response is not linear and nobody should assume it is
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.
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