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.

Comparing SURMOUNT-2 (Lancet, 2023) with SURMOUNT-4 (JAMA, 2024) and finding the comparison harder than it looks.

Different populations, different durations, different endpoints defined slightly differently, and in one case a different estimand. People compare the headline percentages anyway, including me until recently.

Is there a defensible way to put these side by side, or is the honest answer that there is not and we should stop?

Two things before anyone answers the substance.

First, the context in the first post is clear and specific. Second, the question is framed so that an answer can actually address it. Both are the norm here and both matter more than they sound.

post #12 is right about the mechanism and I think understates the practical bit.

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.

Fasting instructions are not optional advice. Taking the tablet with food or with more than a sip of water measurably reduces absorption. This is the one compound in the class where the instructions genuinely determine the exposure.

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.