[Discussion] mechanism is doing more work than we give it credit for
Posting this as a discussion rather than a claim: mechanism is doing more work than we give it credit for.
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 citation and I have not made that mistake since.
Spent an evening on the receptor distribution literature and the side-effect map suddenly stopped looking random.
Not medical advice, obviously, and nothing here is approved for human use. One person with a spreadsheet.
best — the order this archive was captured in
Tolerance to the gastric effect develops with continued exposure while the appetite effect largely persists. That single fact explains most of the "it settles but it still works" pattern the side-effect board reports.
I would not read that in vitro number across to a person. The conditions are nothing like physiological.
I would not read that in vitro number across to a person.
This is the concept everything else on this board is downstream of.
The incretin effect is the observation that oral glucose provokes a larger insulin response than intravenous glucose at matched glycaemia, and the difference is mediated by gut hormones. That is the foundation the whole class sits on.
The incretin effect is the observation that oral glucose provokes a larger insulin response than intravenous glucose at matched glycaemia, and the dif
isabela_nilsen is right that mechanism gives direction and not magnitude. Worth pinning.
isabela_nilsen is right that mechanism gives direction and not magnitude.
Disagreeing with this specific inference — that is a preclinical result being read as human pharmacology.
Does the effect persist with continued dosing or does tolerance develop?
Push back: a receptor being expressed in a tissue does not tell you the agonist reaches it at therapeutic exposure.
That conflates receptor affinity with clinical potency. They are related and they are not the same thing.
- 1The incretin effect is the observation that oral glucose provokes a larger…6 comments in this branch · started by u/isabela_nilsen