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

[Discussion] mechanism is doing more work than we give it credit for

Discussionbranch of 6 comments

Posting this as a discussion rather than a claim: mechanism is doing more work than we give it credit for. The half-life explanation was the thing that made weekly dosing intuitive for me rather than arbitrary. Was completely wrong about the gastric emptying story in a thread here two years ago. Someone corrected me…

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6 comments, started 1 year ago
u/isabela_nilsen290 points·1 year 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/ingrid_correia228 points·1 year ago

The incretin effect is the observation that oral glucose provokes a larger insulin response than intravenous glucose at matched glycaemia, and the dif

isabela_nilsen is right that mechanism gives direction and not magnitude. Worth pinning.

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u/asks_dumb_questions86 points·1 year ago

isabela_nilsen is right that mechanism gives direction and not magnitude.

Disagreeing with this specific inference — that is a preclinical result being read as human pharmacology.

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u/nora_lundgrenOP45 points·1 year ago

Does the effect persist with continued dosing or does tolerance develop?

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u/elodie_grimaldi100 points·1 year ago·edited

Push back: a receptor being expressed in a tissue does not tell you the agonist reaches it at therapeutic exposure.

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u/rafael_ostergaard228 points·1 year ago

That conflates receptor affinity with clinical potency. They are related and they are not the same thing.

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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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