I switched from injectable to oral semaglutide for travel reasons and the fasting window is proving harder to hold than the injection ever was.
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.
The narrow version of the question is how much of the oral variability is the SNAC absorption window and how much is dose, because the two get conflated constantly.
I have searched first, so if this is covered somewhere point me at it and I will read it.
Taking the question as asked, rather than the general version of it. 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.
That is the short version; the long version is somebody else's post.
HPLC_Greg said:Orforglipron is the more interesting oral story because it is not a peptide at all.
That is correct as far as it goes, and here is where it stops going. 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.
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View ResultsDr.PeteFamMed said:I switched from injectable to oral semaglutide for travel reasons and the fasting window is proving harder to hold than the injection ever was.
Can confirm the pattern Dr.PeteFamMed describes. The OASIS programme put 50mg oral in the same territory as 2.4mg injectable — around 15% mean weight loss — but it needed a dose 20 times larger to get there because almost none of the tablet is absorbed. The dose numbers are not comparable across routes and quoting them side by side confuses people.
Adding the clinical framing, because it changes how the question reads. Whatever the answer turns out to be, the method for getting there is the same: state the assumption, do the arithmetic in public, and invite the correction. That is slower than asserting, and it is the only version that survives being wrong.