This is a continuation of a long topic, addressed by post number rather than by page. Start at post 1.
I read post #89 twice before replying, because I had assumed the opposite.
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.
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?
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.
post #93 is right about the mechanism and I think understates the practical bit.
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.
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.
On post #93 — 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.
post #97 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.
Worth separating two things that post #97 runs together.
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?
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.
This follows post #101 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.
On post #101 — 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.
post #105 answers the question as asked. The question underneath it is different.
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.
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.
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.
post #109 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.
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.
I read post #110 twice before replying, because I had assumed the opposite.
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.
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.
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.
Practical note that does not fit anywhere else. Whatever you conclude from this topic, write down what you did and when. The single most useful thing in your own records is not any individual result; it is that they are dated and consecutive.
post #116 answers the question as asked. The question underneath it is different.
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.
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.
| Topic | Participants | Replies | Views | Activity |
|---|---|---|---|---|
|
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…
|
+20 | 24 | 8.7k | 16mo |
|
Journal club: SURPASS-2 and the semaglutide 1 mg comparator
On the subject in the title: Journal club: SURPASS-2 and the semaglutide 1 mg comparator Working notes rather than a conclusion. Session topic: SELECT ( N Engl J Med , 2023). Please read it before posting;…
|
+71 | 76 | 52k | 21mo |
|
Journal club: SURMOUNT-4 and continuation versus withdrawal
Journal club: SURMOUNT-4 and continuation versus withdrawal — setting out what I have, and where I think it stops being reliable. I have seen FLOW ( N Engl J Med , 2024) cited in support of a claim I do not…
|
+32 | 36 | 31k | 3mo |
|
Journal club: STEP-HFpEF and symptom endpoints
Journal club: STEP-HFpEF and symptom endpoints — setting out what I have, and where I think it stops being reliable. Comparing SURMOUNT-2 ( Lancet , 2023) with SURMOUNT-1 ( N Engl J Med , 2022) and finding…
|
+18 | 22 | 2.5k | 11mo |
|
Journal club: the CagriSema phase 2 combination paper
On the subject in the title: Journal club: the CagriSema phase 2 combination 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…
|
2 | 329 | 21h |
| Topic | Participants | Replies | Views | Activity |
|---|---|---|---|---|
|
[2026 update] Confounding by indication, explained with a concrete example
Confounding by indication, explained with a concrete example Writing it up because I had to work it out twice and would rather nobody else did. I have seen SURPASS-4 ( Lancet , 2021) cited in support of a…
|
+103 | 116 | 22k | 5mo |
|
How to read a phase 2 result without treating it as a phase 3 result
The question in the title: How to read a phase 2 result without treating it as a phase 3 result I will give what I have already checked below so nobody repeats it. Session topic: FLOW ( N Engl J Med , 2024).…
|
+36 | 40 | 35k | 7mo |
|
A plateau that disappeared when I changed how I measured
Posting this under the heading it deserves: A plateau that disappeared when I changed how I measured Everything below is what sits behind that. Longitudinal report with the method stated, because a number…
|
+27 | 31 | 7.2k | 3mo |
|
Coming back to: Prediction intervals and why they are more honest than confidence intervals
Prediction intervals and why they are more honest than confidence intervals Writing it up because I had to work it out twice and would rather nobody else did. Comparing SURMOUNT-OSA ( N Engl J Med , 2024)…
|
2 | 65 | 22mo | |
|
Blinding yourself: practical methods and their limits
On the subject in the title: Blinding yourself: practical methods and their limits Working notes rather than a conclusion. Comparing PIONEER 6 ( N Engl J Med , 2019) with STEP 4 ( JAMA , 2021) and finding the…
|
+40 | 44 | 33k | 5d |