Oral versus injectable exposure: comparing apples to a different fruit — a second dataset

The opening post is right about the mechanism and I think understates the practical bit.

Missed doses behave differently for a daily oral than for a weekly injection. With a short interval you are near a trough rather than perturbing a slowly moving average, and the labelling reflects that.

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.

I have written this out at length because the short version keeps being misread.

Post #6 put the caveat in the right place and I want to underline it.

Dose equivalence between oral and injectable formulations is not a simple conversion and no published factor should be used as one. The two were developed and titrated separately.

This is the first time the answer has come with its own limits attached. Appreciated.

The gastrointestinal tolerability profile of the oral formulation is broadly similar in character to the injectable, which supports the effects being systemic rather than local irritation.

I am not the right person to answer the follow-up to this.