Second pass at: Journal club: LEADER as the historical anchor

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.

Worth separating two things that post #20 runs together.

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.

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.

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.

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

Critical appraisal template: (1) What did the trial set out to estimate? (2) Could the design answer that question? (3) Was the population sufficiently similar to your population to apply the results? (4) What was the absolute effect, not just the relative one? (5) What are the two strongest criticisms available?

This follows post #53 rather than contradicting it.

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.

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.

This follows post #62 rather than contradicting it.

For anyone arriving from a search: the marked solution above is the direct answer, and the replies underneath it add the caveats that make it safe to use.

Coming back to post #71, because the follow-up matters more than the original answer.

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.