Oral versus injectable exposure: comparing apples to a different fruit

Oral versus injectable exposure: comparing apples to a different fruit — setting out what I have, and where I think it stops being reliable.

Something about oral versus injectable exposure does not reconcile and I would like a second pair of eyes before I decide which half is wrong.

Two sources, both reputable, giving figures that cannot both be right unless they are measuring different quantities. My suspicion is that they are, and I cannot see how.

PIONEER 6 is the cardiovascular outcome trial for oral semaglutide and it enrolled a diabetes population at high cardiovascular risk. Quoting it outside that population is an extrapolation.

Post #12 answers the question as asked. The question underneath it is different.

Dose numbers for oral formulations are not comparable to injectable ones. The 14 mg oral dose is not equivalent to any injectable dose in the traditional comparison sense. They are different formulations with different pharmacokinetics and cannot be put on the same scale.

Storage for a small molecule is a different problem from storage for a peptide: generally more robust, generally less temperature-sensitive, and generally more affected by humidity.

This is where my knowledge stops and I would rather mark the edge than blur it.

PIONEER 6 was a cardiovascular safety trial for oral semaglutide, not an efficacy trial. Non-inferiority for safety was demonstrated. The point estimates favoured the drug but the trial was not designed to establish benefit.