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c/glp1science·submitted 2 years ago by u/signe_boateng

[Meta] proposal — a flair for gastric emptying posts

Discussionbranch of 6 comments

Proposal, not a decision: proposal — a flair for gastric emptying posts. Went looking for human data on a mechanism everybody here asserts. Found preclinical work and one small study. That was clarifying. Tried to build a mental model from mechanism alone and produced a confident prediction that the trial data flatly…

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6 comments, started 2 years ago
u/maintenance_mode_maxmaintenance169 points·2 years ago

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.

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u/wholesome_lurker142 points·2 years 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/elodie_grimaldi114 points·2 years ago

Correction: that is glucose-dependent insulin secretion, which is why hypoglycaemia risk is low as monotherapy. Not the same claim as you made.

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u/bastian_ekstrom74 points·2 years ago

Agreed — the incretin effect is the load-bearing concept and everything downstream reads differently once you have it.

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[removed]51 points·2 years ago

[removed by moderator]

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u/analog_alphabet29 points·2 years ago

Agreed that receptor distribution is the key to the side-effect map. It is not a mystery, it is anatomy.

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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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