[Discussion] appetite is doing more work than we give it credit for
Something I keep coming back to: appetite is doing more work than we give it credit for. Asked a question here that I thought was stupid and got three papers back. Best thread I have been in on this site. The GIP question, which is the most interesting unsettled thing in this field. Dual agonism at GIP and GLP-1…
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.
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GIP is the arm people argue about because the biology is genuinely unsettled
I would not read that in vitro number across to a person. The conditions are nothing like physiological.
I would not read that in vitro number across to a person.
This is the concept everything else on this board is downstream of.
Small fix — it slows gastric emptying, it does not halt it, and the distinction matters for the mechanism you are proposing.
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.
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.
Disagreeing with this specific inference — that is a preclinical result being read as human pharmacology.
Tried to build a mental model from mechanism alone and produced a confident prediction that the trial data flatly contradicted.
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.