A reference post rather than a discussion. Corrections are the point; I would rather this be right than mine. It is about oral semaglutide, and it is deliberately narrow — everything I am not confident about is marked as such.
What is actually established
Orforglipron is the more interesting oral story because it is not a peptide at all. Being a small molecule it does not need SNAC, does not need the fasting window, and has oral bioavailability in the tens of percent rather than about one.
The condition it depends on
The absorption variability is real, but it partly averages out over weeks — the steady-state trough is less erratic than any single day would suggest. Where it bites is in the first fortnight, when people conclude the tablet does nothing.
The practical version
The practical numbers: about 1% oral bioavailability, 30 minutes fasted before food, no more than 120ml of plain water, and coffee counts as food for this purpose.
What I am not sure about
What I actually want to know is how much of the oral variability is the SNAC absorption window and how much is dose, because the two get conflated constantly. Not looking for reassurance. Looking for the part I have got wrong.
— RegAffairsDC · corrections welcome and will be edited into this post with credit