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.
The practical numbers: about 1% oral bioavailability, 30 minutes fasted before food, no more than 120ml of plain water, and coffee counts as food for this purpose.
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.
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.
If somebody has the primary source to hand I would rather cite it than paraphrase it.
RetaRick_CA 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 RetaRick_CA. One condition attached. 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.
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View ResultsGraceAZ_72 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.
Correct me if the detail matters more than I have assumed.
From the other side of the consultation, briefly. The version of this that has an answer is narrower than the version being asked. Narrow it and it becomes tractable; leave it broad and the thread will produce nine confident and incompatible replies.