Read the primary source rather than the write-up and the two do not agree, so here is what is actually in it.
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.
Where I think it is weakest: the completion rate deserves as much attention as the headline, because a large effect among those who finished is a different claim from a large effect among those enrolled.
What I actually want to know is how much of the SELECT benefit is plausibly independent of the weight loss, and whether that distinction changes anything practical. Happy to be told the question itself is wrong.
Dr.CardioMD 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, though "tolerable" needs defining. A dose you tolerate by eating almost nothing is not tolerated, it is being paid for somewhere else — usually in lean mass, sometimes in adherence three months later.
Dr.CardioMD 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…
I read this differently from Dr.CardioMD, 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.
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Browse GL BiochemTaking the question as asked, rather than the general version of it. Steady state is the thing most people miss. The terminal half-life is about a week, so every dose step takes four to five weeks to fully express itself. Judging a step at day ten is judging the ascent, not the plateau, and it is the single commonest reason people escalate before they needed to.
Dr.SportsMedIN said:Agreed, though "tolerable" needs defining.
All true, with one condition: that curve is for people who reached the dose on schedule. Anyone who slowed the ladder for tolerability is on a different, flatter curve, and comparing yourself with the published mean will make you feel like a non-responder when you are not.