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

incretin: what the trials say vs what this community says

Speculationbranch of 7 comments

incretin: what the trials say vs what this community says. Making the case below, and I expect to lose some of it in the comments. Long half-life in this class comes from structural modification that promotes albumin binding and resists enzymatic degradation. Weekly dosing is a consequence of the molecule, not a…

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7 comments, started 2 months ago
u/sig_figs_sammod · analytical90 points·2 months 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/georgi_chowdhury41 points·2 months ago

Receptor expression in a tissue is necessary but not sufficient for an effect.

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

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u/titration_marshalmod · c/semaglutide47 points·2 months ago

Glucose-dependent insulin secretion is why hypoglycaemia risk is low as monotherapy: the effect scales with glycaemia rather than acting unconditionally.

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u/enzo_petrescu29 points·2 months 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/rasmus_kimani13 points·2 months ago

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

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u/zeynep_villalobos8 points·2 months 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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u/sanne_delgado33 points·2 months ago

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

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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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