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

Journal club: SURPASS-2 and the semaglutide 1 mg comparator Writing it up because I had to work it out twice and would rather nobody else did.

Session topic: SURPASS-2 (N Engl J Med, 2021). Please read it before posting; the discussion is much better when everyone has.

The question I would like us to start with is what the trial set out to estimate, rather than what it found. Once that is on the table we can talk about whether the design could have answered it, and only then about the numbers.

Specific things I would like covered: the population and how far it generalises, how discontinuation was handled, whether the comparator was a fair one, and what the absolute rather than relative effect looks like.

I will summarise at the end and the summary will feed the relevant digest page.

The opening post describes the usual case. This is about the unusual one.

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.

Post #44 and I disagree about the size of the effect, not about the direction.

The arithmetic on SURPASS-2 is the easy part and it is where the errors are, which is an uncomfortable combination. Show your working and someone will catch it.

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.

This is the sort of exchange that makes the archive worth searching.

Fine by me. I had wanted a stronger conclusion and there is not one available.

I had written a reply contradicting post #70 and deleted it. Here is what survived.

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.

What I would tell a new member reading about SURPASS-2 for the first time: the confident posts are not the reliable ones, and the reliable ones are longer.

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.

Not a strong opinion, just a consistent one.