[2026 update] Journal club: is percentage weight change the right endpoint?

Journal club: is percentage weight change the right endpoint? — that is the question, and I have not found it answered plainly anywhere I have looked.

Comparing SURPASS-2 (N Engl J Med, 2021) with SURMOUNT-1 (N Engl J Med, 2022) 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?

post #4 answers the question as asked. The question underneath it is different.

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.

Worth separating two things that post #9 runs together.

SURMOUNT-OSA (N Engl J Med 2024): Tirzepatide in obstructive sleep apnoea, using an objective physiological endpoint. Notable because soft endpoints are avoided. Two parallel trials addressed the confounder directly.

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.

Coming back to post #46, because the follow-up matters more than the original answer.

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.

TRIUMPH (ongoing): Retatrutide phase 3. No results yet. Nothing should be attributed to it because it has not finished. When it does, this discussion will return to it.

SURMOUNT-1 (N Engl J Med 2022): Tirzepatide obesity trial. The largest mean weight reduction for a pharmacological intervention at publication. Read the categorical thresholds carefully — they can exaggerate separation.

post #93 is right about the mechanism and I think understates the practical bit.

Session format: read the paper before posting. The discussion is much better when everyone has. Start with the estimand and population, then methods, then results, then limitations. That order makes critique coherent.

Session format: read the paper before posting. The discussion is much better when everyone has. Start with the estimand and population, then methods, then results, then limitations. That order makes critique coherent.