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c/glp1science·submitted 23 days ago by u/camila_kowalski

[Needs Source] "it heals your metabolism" is not a mechanism

Needs Sourcebranch of 8 comments

"it heals your metabolism" is not a mechanism. It is the sort of thing everyone half-believes and nobody writes down. 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…

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8 comments, started 23 days ago
u/gastric_emptying_g-26 points·23 days ago

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 which the GIP arm contributes — there is a genuine scientific argument about agonism versus antagonism at that receptor, with reasonable people and real data on both sides.

It is worth sitting with that. The clinical effect is not in doubt; the explanation is. That is an ordinary state of affairs in pharmacology and it is a good corrective to the confident mechanistic stories that circulate here.

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u/camila_kowalskiOP-38 points·22 days ago

Is there any human data on that mechanism yet?

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u/hassan_castellanos1 point·22 days ago

Spent an evening on the receptor distribution literature and the side-effect map suddenly stopped looking random.

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[removed]1 point·22 days ago

[removed by moderator]

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u/trialwatch_theoMOD1 point·22 days ago

Speculation is welcome here if it is labelled. This one has been relabelled rather than removed.

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u/camila_kowalskiOP1 point·22 days ago

What was the exposure in that experiment relative to therapeutic?

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u/gustav_vermeulen1 point·22 days ago

receptor agonism is not the same as receptor activation in every tissue

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u/aksel_palacios1 point·22 days ago

GIP is the arm people argue about because the biology is genuinely unsettled

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