Oral semaglutide bioavailability and its variability between people — a second dataset

Coming back to post #14, because the follow-up matters more than the original answer.

Oral versus injectable exposure: comparing a 14 mg oral dose with a 0.5 mg injectable dose is comparing apples to a different fruit. The oral bioavailability is low enough that dose numbers are an order of magnitude different and not directly comparable.

Trial adherence in an oral trial with strict administration requirements is genuinely worse than trial-published data often suggests. That is why the exposure variability in oral formulations is mentioned repeatedly in the discussions here.

Oral bioavailability is variable between people. Some people absorb well; others absorb poorly. That inter-individual variation is larger than with injectables and is one reason the trial data for oral formulations receives different treatment.

This follows post #45 rather than contradicting it.

Why administration conditions matter for oral semaglutide and not for injectables: the oral formulation depends on a transient pH effect in the stomach. Anything that changes gastric pH or transit time changes absorption. Food does both.

Trial adherence in an oral trial with strict administration requirements is genuinely worse than trial-published data often suggests. That is why the exposure variability in oral formulations is mentioned repeatedly in the discussions here.

I read post #54 twice before replying, because I had assumed the opposite.

Oral versus injectable exposure: comparing a 14 mg oral dose with a 0.5 mg injectable dose is comparing apples to a different fruit. The oral bioavailability is low enough that dose numbers are an order of magnitude different and not directly comparable.

Oral versus injectable exposure: comparing a 14 mg oral dose with a 0.5 mg injectable dose is comparing apples to a different fruit. The oral bioavailability is low enough that dose numbers are an order of magnitude different and not directly comparable.

post #115 answers the question as asked. The question underneath it is different.

I disagree with the reply above, and I think the disagreement is substantive rather than terminological.

The distinction being drawn does not survive when you look at the published data for this specific question. I would be glad to be shown wrong on this, because the version I am arguing against is more convenient.

post #124 is right about the mechanism and I think understates the practical bit.

PIONEER programme is phase 3 for oral semaglutide. The trials cover multiple indications and durations. Reading them requires attention to which trial is which because they are not all the same question.