amy_econ_NJ said:

Orforglipron is the more interesting oral story because it is not a peptide at all.

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

If somebody has the primary source to hand I would rather cite it than paraphrase it.

amy_econ_NJ said:

Orforglipron is the more interesting oral story because it is not a peptide at all.

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.

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.

PeptideChemSF said:

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…

Can confirm. Same sequence, different timescale.