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c/glp1science·submitted 1 year ago by u/camila_kowalski

[Meta] the receptor rule is doing its job and people should stop complaining

Speculationbranch of 6 comments

the receptor rule is doing its job and people should stop complaining, and here is what changes in practice if it goes ahead. 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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6 comments, started 1 year ago
u/laila_almeida220 points·1 year 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/ferran_dahlberg69 points·1 year ago

Is that from a human study or a preclinical model?

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u/niels_roos44 points·1 year ago

Not convinced by the linearity assumption. Dose-response in this class is not linear and the trials show it.

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u/signe_boateng21 points·1 year ago

What was the exposure in that experiment relative to therapeutic?

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u/milan_mensah36 points·1 year ago

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

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u/lurker_for_years51 points·1 year ago

Is that from a human study or a preclinical model?

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

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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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