PharmHunterJen said:

SELECT is the trial that changed the framing of this class, because it was an outcome trial rather than a weight trial: about a 20% relative reduction…

Agreed, with the qualification that SELECT enrolled a secondary-prevention population. Extrapolating a 20% relative reduction to a healthy 35-year-old with a BMI of 31 is not what that trial showed.

Worth separating that from cardiovascular outcomes, which this thread keeps folding into the same question. They behave differently and the advice does not transfer.

Dr.KarenChen said:

Agreed on the mechanism, with the caveat that the head-to-head used semaglutide 1mg, not 2.4mg.

Thank you — that is the clearest version of this I have read, and I have read a lot of them.

PharmHunterJen said:

SELECT is the trial that changed the framing of this class, because it was an outcome trial rather than a weight trial: about a 20% relative reduction…

This is where I part company with the consensus forming above. The "earlier than weight loss explains" argument is weaker than this thread makes it sound. Blood pressure and inflammatory markers move fast and are downstream of early weight loss, so the mechanism is not as cleanly separable as the summaries imply.

Correct me if the detail matters more than I have assumed.

The figures, for anyone assembling their own picture. One habit that pays for itself: post the method alongside the number. A figure without its method cannot be checked, and an unchecked figure is how this community accumulates folklore.

Moderator note: good thread. Keeping it here rather than moving it, because the question is general enough to be useful. Carry on.