SleepDoc_PDX said:

Most of what circulates confidently in this community traces back to one summary of one study, and the qualifier was dropped somewhere in the third…

Coming at SleepDoc_PDX’s question from a different direction. 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 in major adverse cardiovascular events in people with established cardiovascular disease and overweight or obesity, without diabetes. The effect appeared earlier than the weight-loss curve can comfortably explain, which is the basis for arguing that some of the benefit is direct — anti-inflammatory and vascular — rather than purely a consequence of weight.

If somebody has the primary source to hand I would rather cite it than paraphrase it.

Adding the numbers, since they settle part of this. Say what you would expect to see if you were wrong, before you look. It is a small discipline and it changes what you notice.

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

A narrower follow-up, since the general answer is now clear:

How much of the between-person variation is pharmacokinetic and how much is just adherence measured badly?

stefan_berlin said:

Say what you would expect to see if you were wrong, before you look.

I read this differently from stefan_berlin, on substance rather than tone. 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.

stefan_berlin said:

Say what you would expect to see if you were wrong, before you look.

That holds where the measurement is reliable. Where it is noisy — and a lot of what gets tracked here is noisy — the same reasoning produces confident nonsense.