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c/glp1science·submitted 2 months ago by u/karma_irrelevant

[Discussion] we are measuring appetite at the wrong time and calling it noise

Discussionbranch of 9 comments

Thinking out loud about this: we are measuring appetite at the wrong time and calling it noise. 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. What is not settled is the mechanism by…

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9 comments, started 2 months ago
u/karma_irrelevant82 points·2 months ago·edited

I would not read that in vitro number across to a person. The conditions are nothing like physiological.

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u/ilias_kaufmann23 points·2 months 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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u/niels_roos8 points·2 months ago

incretin effect first, then everything else in this board makes sense

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u/karma_irrelevantOP5 points·2 months ago

albumin binding is most of the half-life story

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[deleted]2 points·2 months ago

[deleted]

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u/flair_enthusiast48 points·2 months 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/tomas_broberg31 points·2 months ago

Disagree. That is a preclinical finding in a rodent model and you are stating it as human pharmacology.

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u/camila_mensa14 points·2 months ago·edited

Disagree.

Adding the caveat the paper itself makes in its limitations section, which is stronger than anything in this thread.

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u/ireland_drugs_pay25 points·2 months ago

the peripheral and central stories are not in competition

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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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