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c/glp1science·submitted 1 year ago by u/santiago_rasmussen

the appetite question that gets asked weekly, answered properly

Questionbranch of 6 comments

the appetite question that gets asked weekly, answered properly. Change my mind, genuinely — I have no stake in being right about this. The GIP question, which is the most interesting unsettled thing in this field. Dual agonism at GIP and GLP-1 receptors produces clinical results that are robust and well replicated.…

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6 comments, started 1 year ago
u/zeynep_villalobos117 points·1 year ago

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.

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u/santiago_rasmussenOP138 points·1 year ago

Tried to build a mental model from mechanism alone and produced a confident prediction that the trial data flatly contradicted.

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u/niels_roos31 points·1 year ago

Yes. The central component is the one that explains the reports on this site better than gastric emptying does.

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u/wholesome_lurker36 points·1 year ago

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.

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u/rina_bergstrom9 points·1 year ago

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.

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u/plain_titration11 points·1 year ago

This. Albumin binding and modification are why the half-life is what it is, and it is a design decision rather than an accident.

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The mechanism layer: incretin physiology, receptor distribution, gastric emptying, central appetite signalling, glucagon-receptor contribution, amylin co-agonism, and the pharmacokinetics that make weekly dosing possible. Papers get cited by journal and year or they get a [needs source] reply.

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