Posting this because the summary going around does not say what the paper says, and the difference matters for how people here are using 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 population was selected and supported in ways a real cohort is not, so I would read the effect size as a ceiling rather than an expectation.
The narrow version of the question is how much of the SELECT benefit is plausibly independent of the weight loss, and whether that distinction changes anything practical. I would rather have one careful answer than five confident ones.
nancy_portland 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…
True, though the ladder is longer and that is not a neutral detail — six dose steps means six opportunities to stall on the way up, and plenty of people never reach the dose the headline number came from.
nancy_portland 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 nancy_portland, 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 BiochemAnswering the narrow version, because the broad one does not have a single answer. Steady state is faster than people expect: half-life about five days, so you are at plateau in roughly three to four weeks rather than five. That matters when you are deciding whether a dose step has finished expressing itself.
Dr.CardioMD said:True, though the ladder is longer and that is not a neutral detail — six dose steps means six opportunities to stall on the way up, and plenty of…
Mine went the same way, slower. Posting only so the count is not one.