This is a continuation of a long topic, addressed by post number rather than by page. Start at post 1.
SURPASS-2 sits at the boundary between what this community can usefully discuss and what it cannot, and I think it falls on the discussable side, narrowly.
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.
The part I am sure of is shorter than the part I have written.
Fine by me. I had wanted a stronger conclusion and there is not one available.
I had written a reply contradicting post #61 and deleted it. Here is what survived.
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.
The most common failure mode is spending fifty minutes on the effect size and ten on the population. Reversing that ratio would improve most sessions.
I am confident about the direction and much less about the magnitude.
Post #69 is the version of this I will quote in future. One addition.
The figures usually contain the finding and the text usually contains the interpretation. Separating them for the first twenty minutes is a discipline worth keeping.
Confirming post #68 from a second method, which matters more than confirming it from a second person.
On SURPASS-2: the maintained page in the documentation commons covers the general case with citations and a review date, which is more reliable than any reply here including this one.
I had written a reply contradicting post #70 and deleted it. Here is what survived.
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.
Sessions on negative or null results are consistently the most instructive and the hardest to get anyone to attend.
Where the group cannot agree, record the disagreement rather than resolving it by seniority. The recorded disagreement is more honest and more useful later.
The confident answers on SURPASS-2 and the well-sourced answers are not the same answers, which is the most useful thing I have learned reading this category.
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.
Reading it again, the caveat matters more than the finding.
Marking my uncertainty on SURPASS-2 explicitly. I am confident about the direction, much less confident about the size, and not confident at all that it generalises past the case in the first post.
Coming back to post #79, because the follow-up matters more than the original answer.
Filing a mild objection to the consensus on SURPASS-2. Mild because I might be wrong; an objection because nobody has addressed the case that does not fit.
Post #79 is right about the mechanism and I think understates the practical bit.
Reading order that works for these sessions: registry entry, methods, baseline table, primary result, then abstract last. Reading the abstract first anchors everything that follows.
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.
Anyone who has looked at this more carefully, please correct the record.
That matches what I have seen, for whatever a single anecdote is worth.
Post #83 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.
I looked this up rather than remembered it, which is the right order.
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.
The answer changed when I changed how I was measuring, which was informative.