julia.endo said:

Oral semaglutide is absorbed in the stomach with the help of SNAC, which locally raises pH and protects the peptide long enough to cross.

I do not accept that the fasting window is a minor inconvenience. Adherence data on daily orals with timing requirements is consistently worse than weekly injections, and a drug you take imperfectly is a lower dose than the one on the box.

The figures, for anyone assembling their own picture. For anyone assembling their own picture: Tmax is one to three days, terminal half-life about 165 to 170 hours, steady state at four to five weeks, and subcutaneous bioavailability near 89%. Those four numbers explain most of the questions people ask about timing.

Correct me if the detail matters more than I have assumed.

anders_CPH said:

I do not accept that the fasting window is a minor inconvenience.

Coming at anders_CPH’s question from a different direction. The dose-response is real but shallow at the top. Across STEP 1 and STEP 4 the gap between 1.7mg and 2.4mg is a couple of percentage points of body weight on average, and the average is carrying a wide spread — plenty of people at 1.7mg sit above the 2.4mg mean. If a dose is working and tolerable, "working" is the relevant variable, not "maximal".

A narrower follow-up, since the general answer is now clear:

How much of the oral variability is the SNAC absorption window and how much is dose, because the two get conflated constantly?

Reporting back.

Update — I went back to the injectable. Not because the tablet did not work, but because the fasting window and my mornings were never going to agree.