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.

PharmacoVig_BOS 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.

Agreeing with PharmacoVig_BOS, and the qualification matters more than the agreement. Worth adding that the tablet is taken daily, so a missed dose costs far less than a missed weekly injection. That is a genuine advantage nobody lists.

jason_paloalto 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.

This matches mine closely enough to be worth saying so. 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.

Clinical perspective, offered as context rather than as advice. Start from the measurement rather than the conclusion. Almost every disagreement here turns out to be two people measuring different things and comparing the numbers anyway.