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

does half-life actually matter or is it forum lore at this point

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does half-life actually matter or is it forum lore at this point. If this has been answered properly somewhere, link me and I will delete. 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…

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8 comments, started 2 years ago
u/laila_almeida679 points·2 years ago

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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[removed]250 points·2 years ago

[removed by moderator]

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u/milan_mensah157 points·2 years ago·edited

The incretin effect is the observation that oral glucose provokes a larger insulin response than intravenous glucose at matched glycaemia, and the difference is mediated by gut hormones. That is the foundation the whole class sits on.

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u/wholesome_lurkerOP111 points·2 years ago

That study was in a rodent model. Worth stating, since the thread has been reading it as human data.

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u/whois_wanda42 points·2 years ago

Right — mechanism gives you a direction. It never gives you an effect size and people use it as though it does.

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u/aa_analysis_andy318 points·2 years ago

Tolerance to the gastric effect develops with continued exposure while the appetite effect largely persists.

Agreed — and it is why the central and peripheral stories are complementary rather than rival.

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u/wholesome_lurkerOP144 points·2 years ago

albumin binding is most of the half-life story

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u/georgi_chowdhury74 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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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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