Putting this up for argument rather than for agreement. I have read it twice and I am still not certain what it supports.
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 comparator does most of the work in how this gets reported, and it is not the comparator most people think they are citing.
What I am trying to establish is how much of the oral variability is the SNAC absorption window and how much is dose, because the two get conflated constantly. I have searched first, so if this is covered somewhere point me at it and I will read it.
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.
sarah.morrison 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 sarah.morrison. 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.
sarah.morrison 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.
That is the short version; the long version is somebody else's post.
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View ResultsThis one has a reasonably settled answer, so here it is. 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.
MikeFit_NJ said:Orforglipron is the more interesting oral story because it is not a peptide at all.
Second this. I had assumed I was the exception until I read this.