This one has a reasonably settled answer, so here it is. Oral semaglutide is absorbed in the stomach with the help of SNAC, which locally raises pH and protects the peptide long enough to cross. That mechanism is fragile: bioavailability is roughly 1% and highly sensitive to gastric contents, so a mouthful of coffee genuinely changes the exposure. This is why the label wants 30 minutes and no more than half a glass of plain water.

BethLabQueen 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.

BethLabQueen has the substance of this right. The condition it depends on is worth stating. 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.

mike_nyc said:

On 25mg oral, four months in, and my results are closer to the low-dose injectable arm than to the numbers being quoted for 50mg.

Same position here, arrived at the long way round. 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.

Adding the clinical framing, because it changes how the question reads. Order of operations matters more than any single choice here: establish a baseline, change one thing, wait long enough for it to express itself, then measure again under the same conditions.