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.
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Evidence · Journal club · continued
Journal club: SURMOUNT-1, read without the press release posts 61–90
This is a continuation of a long topic, addressed by post number rather than by page. Start at post 1.
post #61 is right about the mechanism and I think understates the practical bit.
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.
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i.rasmussen, post #2: 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. Go to post
I read post #61 twice before replying, because I had assumed the opposite.
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.
Thank you for the correction. I have edited my earlier post with a note rather than silently, so the thread still makes sense to read. The error was mine and it was the kind that comes from remembering a figure instead of looking it up.
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i.rasmussen, post #61: 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. Go to post
Coming back to post #65, because the follow-up matters more than the original answer.
Having read the exchange above, I think I was wrong earlier in this topic and I want to say so plainly rather than quietly editing.
The correction was fair and I had been repeating something I had not checked carefully enough.
Picking up post #65: that is the part I would want checked first.
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.
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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.
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n.rahimi, post #10: post #9 answers the question as asked. The question underneath it is different. 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. Go to post
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.
This follows post #68 rather than contradicting 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.
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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.
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revision_history, post #30: post #29 answers the question as asked. The question underneath it is different. 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. Go to post
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.
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.
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a.reyes, post #15: Thank you for the correction. I have edited my earlier post with a note rather than silently, so the thread still makes sense to read. The error was mine and it was the kind that comes from remembering a figure instead of looking it up. Go to post
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.
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.
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On post #74 — agreed on the reasoning, with one qualification.
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.
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m.dalgaard, post #24: Picking up post #21: that is the part I would want checked first. 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. Go to post
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.
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?
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On post #79 — agreed on the reasoning, with one qualification.
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.
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a.ilunga, post #78: On post #74 — agreed on the reasoning, with one qualification. 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. Go to post
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.
Collapsed as off-topic by two members at trust level 3 or above
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?
Worth separating two things that post #83 runs together.
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.
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c.okafor, post #73: 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. Go to post
post #87 is right about the mechanism and I think understates the practical bit.
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.
j.baptista, post #36: 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. Go to post
Coming back to post #87, because the follow-up matters more than the original answer.
Having read the exchange above, I think I was wrong earlier in this topic and I want to say so plainly rather than quietly editing.
The correction was fair and I had been repeating something I had not checked carefully enough.
Picking up post #87: that is the part I would want checked first.
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.
2 likes 16mo