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

Confirming post #13 from a second method, which matters more than confirming it from a second person.

SURPASS-2 has a well-known answer and a correct answer, and the interesting work is establishing that they are the same. Nobody has done that here yet.

The claim about SURPASS-2 upthread is stronger than its source supports. I have read the source. The source says "associated with" and the post says "causes".

The figures usually contain the finding and the text usually contains the interpretation. Separating them for the first twenty minutes is a discipline worth keeping.

Post #16 describes the usual case. This is about the unusual one.

STEP 1 (N Engl J Med 2021): The pivotal obesity trial for semaglutide and the reference point for most subsequent comparison. Mean weight reduction was substantially larger than anything previously achieved pharmacologically.

Narrowing post #18, because the general version has more than one answer.

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.

Everything in post #16 holds. The case it does not cover is the one I have.

Something worth flagging about SURPASS-2: the strongest-sounding claims in this thread are the ones with no source attached, which is the usual pattern and not a coincidence.

Answering the question post #17 raises rather than the one it answers.

Where the group cannot agree, record the disagreement rather than resolving it by seniority. The recorded disagreement is more honest and more useful later.

The useful distinction on SURPASS-2 is between what was measured and what was inferred from it. Both end up in the same sentence and only one of them has error bars.

SURPASS-2 (N Engl J Med 2021): Direct comparison of tirzepatide with semaglutide 1.0 mg. The 1.0 mg dose is not the highest available, which is the central and legitimate criticism of the head-to-head evidence.

That is my reading. Someone else read the same page differently and was reasonable.

A request rather than an answer: could whoever has the primary source for SURPASS-2 post it? I have seen the claim three times this month and each version had lost a qualifier.

Two claims get bundled together under SURPASS-2 and they need separating. The descriptive one — this is what was observed — is usually well supported. The causal one — this is why — usually is not.

Almost every disagreement in threads like this one dissolves once you say which of the two you are making.

Adding a data point of agreement rather than a data point.

The baseline characteristics table is the single most useful page for the questions that get asked here, because it tells you who the result applies to.

Second-hand, so weight it accordingly.

Post #25 is the version of this I will quote in future. One addition.

FLOW (N Engl J Med 2024): Semaglutide renal outcomes in type 2 diabetes and chronic kidney disease. Stopped early for efficacy. Component-by-component analysis is essential because the components differ in how patient-important they are.

Two things can be true about SURPASS-2 at once: the mechanism is plausible and the evidence for the size of the effect is thin. Most of the argument here is people defending the first against attacks on the second.

Picking up post #29: that is the part I would want checked first.

STEP 1 (N Engl J Med 2021): The pivotal obesity trial for semaglutide and the reference point for most subsequent comparison. Mean weight reduction was substantially larger than anything previously achieved pharmacologically.

It is worth checking rather than assuming, which costs nothing.