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

the appetite question that gets asked weekly, answered properly

Questionbranch of 10 comments

the appetite question that gets asked weekly, answered properly. Change my mind, genuinely — I have no stake in being right about this. The GIP question, which is the most interesting unsettled thing in this field. Dual agonism at GIP and GLP-1 receptors produces clinical results that are robust and well replicated.…

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10 comments, started 1 year ago
u/rafael_ostergaard40 points·1 year ago

Went looking for human data on a mechanism everybody here asserts. Found preclinical work and one small study. That was clarifying.

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u/nora_lundgren11 points·1 year ago

Is there any human data on that mechanism yet?

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u/santiago_rasmussenOP-6 points·1 year ago

Is that from a human study or a preclinical model?

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u/viktor_girard1 point·1 year ago

Do you have the paper, or a summary of it?

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u/elodie_grimaldi-7 points·1 year ago

The half-life explanation was the thing that made weekly dosing intuitive for me rather than arbitrary.

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u/trialwatch_theotrial nerd10 points·1 year ago

Why mechanism talk keeps misleading people, including me.

A mechanism tells you a direction. It does not tell you a magnitude, a timescale, or whether the pathway is operative at the exposures involved. "Receptor X is expressed in tissue Y" is a fact; "therefore effect Z in a person" is a hypothesis with several missing steps.

The corrective is boring and it works: ask whether the evidence is preclinical or human, ask what exposure was used, and read the limitations section before the abstract. Most of the confidently wrong posts on this board — several of them mine — skipped all three.

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u/santiago_rasmussenOP6 points·1 year ago

gastric emptying slows, it does not stop

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u/enzo_danquah3 points·1 year ago

the central appetite effect is doing more work than the gut effect

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u/kian_balogun4 points·1 year ago

preclinical is not clinical and rodents are not small people

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u/gastric_emptying_g2 points·1 year ago·edited

preclinical is not clinical and rodents are not small people

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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