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c/glp1science·submitted 8 months ago by u/ismael_eriksen

reading pharmacology threads from 2024 and half of it aged badly

Speculationbranch of 9 comments

reading pharmacology threads from 2024 and half of it aged badly — a position I have arrived at slowly and would like tested. The half-life explanation was the thing that made weekly dosing intuitive for me rather than arbitrary. Started reading limitations sections first. It has changed how much weight I give to…

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9 comments, started 7 months ago
u/georgi_chowdhury513 points·7 months ago

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 explanation for sustained intake reduction.

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u/camila_lindqvist-18 points·7 months ago

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/ferran_batista1 point·7 months ago·edited

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

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u/brigade_detector1 point·7 months ago

Agreed that receptor distribution is the key to the side-effect map. It is not a mystery, it is anatomy.

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u/viktor_girard1 point·7 months ago

preclinical is not clinical and rodents are not small people

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u/flair_enthusiast1 point·7 months ago

albumin binding is most of the half-life story

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u/ingrid_correia1 point·7 months ago

read the discussion section, that is where the honesty lives

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u/rafael_ostergaard1 point·7 months ago

mechanism explains a direction, not a magnitude

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u/marisol_kravchenko1 point·7 months ago

the peripheral and central stories are not in competition

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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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