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. It is the kind of thing that is obvious once and never again.
Journal club: semaglutide in MASH, and surrogate endpoints — does this still hold? I have a specific reason for asking rather than idle curiosity, and the context is below.
A narrow question about semaglutide in MASH, deliberately narrow, because the broad version has been asked here four times and produced four long threads and no answer.
One question, stated units, stated method, and what I have already ruled out.
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.
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.
It is the kind of thing that is obvious once and never again.
Picking up the opening post: that is the part I would want checked first.
SOUL (N Engl J Med 2025): Oral semaglutide cardiovascular outcomes. Extends the cardiovascular evidence to the oral formulation. Note that oral bioavailability is lower and more variable than injectable.
I would put a moderate confidence on that and no more.
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About the Journal club category
Our recurring session. One named paper per topic, methods first, conclusions last. Everyone reads before posting. This post is a community wiki: any member at trust level 3 or above can edit it, and every…
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+2 | 6 | 12k | 16mo |
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Journal club: what we got wrong in an earlier session
On the subject in the title: Journal club: what we got wrong in an earlier session Working notes rather than a conclusion. Bringing a claim rather than a paper, because the claim is the thing circulating. The…
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+114 | 125 | 2.5k | 23h |
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Journal club: STEP-HFpEF and symptom endpoints — a second dataset
On the subject in the title: Journal club: STEP-HFpEF and symptom endpoints — a second dataset Working notes rather than a conclusion. Posting a small dataset on step-hfpef and symptom endpoints. It is mine,…
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+11 | 15 | 4k | 10mo |
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Journal club: SUSTAIN 6 and its retinopathy signal
On the subject in the title: Journal club: SUSTAIN 6 and its retinopathy signal Working notes rather than a conclusion. Reading SUSTAIN 6 ( N Engl J Med , 2016) for the population rather than the effect,…
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+110 | 122 | 46k | 1d |
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Journal club: SELECT, absolute risk, and how it was reported
Journal club: SELECT, absolute risk, and how it was reported Writing it up because I had to work it out twice and would rather nobody else did. A question about what the numbers mean rather than what they…
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2 | 52k | 1mo |
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Criticising the method without criticising the authors — one year on
On the subject in the title: Criticising the method without criticising the authors — one year on Working notes rather than a conclusion. A methods question rather than a substantive one, about Criticising…
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+16 | 20 | 61k | 11mo |
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Journal club: indirect comparison between two programmes, defended and attacked
Journal club: indirect comparison between two programmes, defended and attacked Writing it up because I had to work it out twice and would rather nobody else did. Trying to work out what would count as…
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+122 | 131 | 5.2k | just now |
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[2026 update] Journal club: FLOW and the renal composite, component by component
Journal club: FLOW and the renal composite, component by component Writing it up because I had to work it out twice and would rather nobody else did. A question about what the numbers mean rather than what…
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2 | 21k | 9d | |
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Second pass at: Retatrutide mass and identity: what a report should show
Second pass at: Retatrutide mass and identity: what a report should show — setting out what I have, and where I think it stops being reliable. Two things I would like separated before anyone answers on…
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+65 | 71 | 4.6k | 13mo |
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Adjudicated events and why the definition matters
On the subject in the title: Adjudicated events and why the definition matters Working notes rather than a conclusion. A follow-up question about adjudicated events that I did not know to ask the first time.…
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2 | 4.5k | 2mo |