Worth separating two things that the opening post runs together.
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.
On post #3 — agreed on the reasoning, with one qualification.
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.
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.
This follows post #8 rather than contradicting it.
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.
Read the full topic (19 posts)
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Follow-up: Journal club: the retatrutide phase 2 obesity paper
On the subject in the title: Journal club: the retatrutide phase 2 obesity paper Working notes rather than a conclusion. I have seen SURMOUNT-1 ( N Engl J Med , 2022) cited in support of a claim I do not…
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+20 | 24 | 8.7k | 16mo |
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Journal club: LEADER as the historical anchor
Journal club: LEADER as the historical anchor Writing it up because I had to work it out twice and would rather nobody else did. Comparing STEP 1 ( N Engl J Med , 2021) with SURMOUNT-4 ( JAMA , 2024) and…
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+103 | 110 | 8.1k | 2h |
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Journal club: SURMOUNT-4 and continuation versus withdrawal — a second dataset
Posting this under the heading it deserves: Journal club: SURMOUNT-4 and continuation versus withdrawal — a second dataset Everything below is what sits behind that. Comparing STEP 8 ( JAMA , 2022) with FLOW…
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+58 | 64 | 17k | 13mo |
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Journal club: STEP 4 and what a withdrawal design can prove — one year on
Journal club: STEP 4 and what a withdrawal design can prove — one year on Writing it up because I had to work it out twice and would rather nobody else did. Session topic: SURMOUNT-OSA ( N Engl J Med , 2024).…
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+56 | 62 | 34k | 15mo |
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Journal club: FLOW and the renal composite, component by component
On the subject in the title: Journal club: FLOW and the renal composite, component by component Working notes rather than a conclusion. Session topic: STEP 2 ( Lancet , 2021). Please read it before posting;…
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+84 | 91 | 18k | 2y |
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Why fasting instructions for oral semaglutide are not optional advice
Why fasting instructions for oral semaglutide are not optional advice I have a specific reason for asking rather than idle curiosity, and the context is below. I have seen SUSTAIN 6 ( N Engl J Med , 2016)…
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+70 | 74 | 1.1k | 23d |
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Semaglutide half-life: where the 165 to 184 hour figure comes from — what changed since
Posting this under the heading it deserves: Semaglutide half-life: where the 165 to 184 hour figure comes from — what changed since Everything below is what sits behind that. Comparing STEP 8 ( JAMA , 2022)…
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+125 | 132 | 39k | 16mo |
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What we do not know about retatrutide, listed explicitly
The question in the title: What we do not know about retatrutide, listed explicitly I will give what I have already checked below so nobody repeats it. Comparing FLOW ( N Engl J Med , 2024) with SURMOUNT-OSA…
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+106 | 113 | 4.8k | 17mo |
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Journal club: orforglipron phase 2 and the non-peptide question
Journal club: orforglipron phase 2 and the non-peptide question Writing it up because I had to work it out twice and would rather nobody else did. I have seen SUSTAIN 6 ( N Engl J Med , 2016) cited in support…
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+120 | 132 | 13k | 1d |
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Retatrutide's phase 2 heart-rate signal and how to think about it — the long version
Retatrutide's phase 2 heart-rate signal and how to think about it — the long version Writing it up because I had to work it out twice and would rather nobody else did. I have seen SURMOUNT-OSA ( N Engl J Med…
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2 | 103 | 17mo |