[Meta] the mechanism rule is doing its job and people should stop complaining
Putting this to the board: the mechanism rule is doing its job and people should stop complaining. 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 with a…
gastric emptying slows, it does not stop
Does the effect persist with continued dosing or does tolerance develop?
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.
Correcting my own comment: I attributed that to the GIP arm and the paper attributes it to the GLP-1 arm.
Right — mechanism gives you a direction. It never gives you an effect size and people use it as though it does.
preclinical is not clinical and rodents are not small people