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 subgroup findings are the part I trust least — with enough subgroups something is always significant, and these were not all pre-registered.
What I am trying to establish is how much of the SELECT benefit is plausibly independent of the weight loss, and whether that distinction changes anything practical. Practical detail welcome, however dull — the duller the better.
Figures above are from the primary publication rather than the press summary. If a number here disagrees with one you have, post yours and we will work out which of us is reading a secondary source.
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…
Pushing back on Dr.CardioMD here. 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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View ResultsThis one has a reasonably settled answer, so here it is. Albumin binding above 99% is the whole reason weekly dosing works, and it is also why the trough matters more than the peak. People who dose late are not losing a peak, they are letting the trough fall, and the appetite effect tracks the trough.
If somebody has the primary source to hand I would rather cite it than paraphrase it.
Dr.RaviCardio 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.