[Meta] the incretin rule is doing its job and people should stop complaining
the incretin rule is doing its job and people should stop complaining. Nothing about this affects the ranking maths, before anyone asks. GIP receptor biology is genuinely unsettled — there is a live argument about agonism versus antagonism at the receptor — and the clinical results are robust regardless, which is an…
Disagree. That is a preclinical finding in a rodent model and you are stating it as human pharmacology.
Retitled to distinguish preclinical from clinical, which the original ran together.
incretin effect first, then everything else in this board makes sense
Does the effect persist with continued dosing or does tolerance develop?
That conflates receptor affinity with clinical potency. They are related and they are not the same thing.
Push back: a receptor being expressed in a tissue does not tell you the agonist reaches it at therapeutic exposure.
Which receptor arm are you attributing that to?
Is there any human data on that mechanism yet?
receptor distribution is why the side effects are where they are
the peripheral and central stories are not in competition
glucagon agonism sounds paradoxical until you read the energy expenditure work
Is that from a human study or a preclinical model?
Was completely wrong about the gastric emptying story in a thread here two years ago. Someone corrected me with a citation and I have not made that mistake since.
Yes. The discussion section is where the authors say what they actually think, and almost nobody here reads it.