[2026 update] Journal club: SURPASS-2 and the semaglutide 1 mg comparator posts 121–139

SELECT (N Engl J Med 2023): Semaglutide cardiovascular outcomes without diabetes. The first outcome trial in people without diabetes, which decoupled the cardiovascular argument from glucose control. Read the absolute numbers, not just the relative reduction.

If that reads as pedantic, it is, and it has saved me twice.

No disagreement from me. Posting only so the question does not look ignored.

Post #121 is right about the mechanism and I think understates the practical bit.

A definition problem is doing most of the work in this SURPASS-2 discussion. Once the term is pinned down I suspect the disagreement mostly goes away and what is left is small.

What I would check first on SURPASS-2 is whether the thing being measured moved or whether the way of measuring it moved. Those look identical in a graph.

The most common failure mode is spending fifty minutes on the effect size and ten on the population. Reversing that ratio would improve most sessions.

That has been true for the cases I have seen and I have not seen many.

PIONEER 6 (N Engl J Med 2019): Cardiovascular safety trial for oral semaglutide, not efficacy. Non-inferiority for safety was met. The trial was not designed to establish benefit, though point estimates favoured the drug.

I have changed my mind on this once already, so take it as current rather than settled.

Confirming post #126 from a second method, which matters more than confirming it from a second person.

The number people quote for SURPASS-2 is a central estimate presented without its interval, and the interval is wide enough that the estimate is nearly uninformative on its own.

The arithmetic in post #126 is right; the assumption feeding it is the part to check.

Reading order that works for these sessions: registry entry, methods, baseline table, primary result, then abstract last. Reading the abstract first anchors everything that follows.

I have kept the units in throughout, for the obvious reason.

SURPASS-2 was covered in the wiki last year and the page has a review date on it, which is a better starting point than my memory of a thread.

What I can speak to on SURPASS-2 is narrow, so I will keep it narrow rather than generalising from it. Beyond that boundary I do not know.

Sessions on negative or null results are consistently the most instructive and the hardest to get anyone to attend.

That is the shape of it. The detail is where I would expect to be corrected.

I read post #131 twice before replying, because I had assumed the opposite.

The most useful reply I ever got about SURPASS-2 was a request to state my units. It sounds like pedantry and it has saved me twice.

This is the answer, and the reason it is the answer is the more useful part.