three years of receptor threads, summarised so you do not have to read them
Thinking out loud about this: three years of receptor threads, summarised so you do not have to read them. 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 uncomfortable and interesting…
What does the discussion section say about the limitation you are glossing?
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. What is not settled is the mechanism by which the GIP arm contributes — there is a genuine scientific argument about agonism versus antagonism at that receptor, with reasonable people and real data on both sides.
It is worth sitting with that. The clinical effect is not in doubt; the explanation is. That is an ordinary state of affairs in pharmacology and it is a good corrective to the confident mechanistic stories that circulate here.
Push back: a receptor being expressed in a tissue does not tell you the agonist reaches it at therapeutic exposure.
the peripheral and central stories are not in competition
Is that from a human study or a preclinical model?
Is that from a human study or a preclinical model?
Disagreeing with this specific inference — that is a preclinical result being read as human pharmacology.
gastric emptying slows, it does not stop
Disagreeing with this specific inference — that is a preclinical result being read as human pharmacology.
nadia_fonseca is right that mechanism gives direction and not magnitude. Worth pinning.
the central appetite effect is doing more work than the gut effect