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.
13 likes 11d
Evidence · Journal club · continued
Journal club: what we got wrong in an earlier session posts 91–120
This is a continuation of a long topic, addressed by post number rather than by page. Start at post 1.
post #91 answers the question as asked. The question underneath it is different.
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.
4 likes 11d
Coming back to post #91, because the follow-up matters more than the original answer.
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.
0 likes 11d
peak_purity, post #68: I read post #66 twice before replying, because I had assumed the opposite. 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?… Go to post
I disagree with the reply above, and I think the disagreement is substantive rather than terminological.
The distinction being drawn does not survive when you look at the published data for this specific question. I would be glad to be shown wrong on this, because the version I am arguing against is more convenient.
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?
8 likes 10d
I read post #95 twice before replying, because I had assumed the opposite.
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.
0 likes 9d
l.solberg, post #61: 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. Go to post
This follows post #95 rather than contradicting it.
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.
f.chowdhury, post #70: On post #66 — agreed on the reasoning, with one qualification. 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
On post #95 — agreed on the reasoning, with one qualification.
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.
a.delgado, post #10: Coming back to post #8, 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. Go to post
Coming back to post #99, because the follow-up matters more than the original answer.
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.
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?
15 likes 8d
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.
3 likes 8d
ma.nascimento, post #21: 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? Go to post
I read post #103 twice before replying, because I had assumed the opposite.
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.
This follows post #103 rather than contradicting it.
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.
10 likes 7d
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.
1 like 7d
bench_peak, post #45: Picking up post #42: that is the part I would want checked first. 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
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.
n.serrano, post #96: 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? Go to post
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.
ai.vukovic, post #72: This follows post #69 rather than contradicting it. 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
Picking up post #107: that is the part I would want checked first.
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.
Collapsed as off-topic by two members at trust level 3 or above
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.
Worth separating two things that post #108 runs together.
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.
1 like 5d
a.vestergaard, post #14: 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
This follows post #110 rather than contradicting it.
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.
post #114 answers the question as asked. The question underneath it is different.
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.
0 likes 4d
On post #112 — agreed on the reasoning, with one qualification.
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.
3 likes 4d
aliquot_line, post #3: post #2 answers the question as asked. The question underneath it is different. 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
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.
Staff post. Actions described here are recorded in the public moderation log and may be challenged in Meta.
post #118 is right about the mechanism and I think understates the practical bit.
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.
24 likes 3d