Journal club: the retatrutide phase 2 obesity paper

Journal club: the retatrutide phase 2 obesity paper — 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 think it supports, twice this month, so I would like to work through what it actually shows.

My reading is that the trial is sound for its own question and is being stretched to answer a different one. I might be wrong about that, which is why this is a topic rather than a correction.

What I would like from this discussion: someone who disagrees with me to say why, with the section of the paper they are relying on.

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.

I read post #3 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.

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.