Posting this because the summary going around does not say what the paper says, and the difference matters for how people here are using it.
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.
Where I think it is weakest: the population was selected and supported in ways a real cohort is not, so I would read the effect size as a ceiling rather than an expectation.
So the question, as narrowly as I can put it: how much of the oral variability is the SNAC absorption window and how much is dose, because the two get conflated constantly. I would rather have one careful answer than five confident ones.
Figures above are from the primary publication rather than the press summary. If a number here disagrees with one you have, post yours and we will work out which of us is reading a secondary source.
PeptideChemSF 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.
No disagreement with PeptideChemSF. One condition attached. 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.
PeptideChemSF 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.
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View ResultsAnswering the narrow version, because the broad one does not have a single answer. 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.
FDA_TrackerJim said:Orforglipron is the more interesting oral story because it is not a peptide at all.
Can confirm. Same sequence, different timescale. Posting only so the count is not one.