carl_compliance 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.

cory_ATX said:

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

Saving this. It is the first explanation that did not require me to already understand it. Printing the relevant bit and taking it with me.

carl_compliance 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…

Filing a mild objection. Mild because I might be wrong; an objection because nobody has addressed the case that does not fit. 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.

Adding the numbers, since they settle part of this. The boring version of this is the one that works, and the boring version is: measure a baseline, change one variable, wait, measure again under the same conditions. Nobody wants that answer and it is still the answer.

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

Moderator note: leaving this open. It is being argued well and the disagreement is the useful part. Thread quality here is what the rules are for. Keep it up.