This gets cited here weekly, usually second-hand, so it is worth setting out what it does and does not establish.
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.
The bit I cannot resolve on my own is how much of the SELECT benefit is plausibly independent of the weight loss, and whether that distinction changes anything practical. I have searched first, so if this is covered somewhere point me at it and I will read it.
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.
PharmHunterJen 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…
NNT calculation for cardiovascular risk clinical endpoints: NNT = 1/ARR (absolute risk reduction).
From SELECT trial: MACE at 39 months — 6.5% semaglutide vs 8.0% placebo. ARR = 1.5%. NNT = 67 over 3.3 years.
Compare to established therapies:
| Intervention | NNT | Timeframe |
|---|---|---|
| Semaglutide (MACE) | 67 | 3.3 years |
| Statins primary prevention (MI) | ~100 | 5 years |
| Aspirin secondary prevention | ~77 | 2 years |
These NNTs are clinically meaningful and comparable to accepted cardiovascular interventions.
PharmHunterJen 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 PharmHunterJen, 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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View Resultspete_manc_UK said:The "earlier than weight loss explains" argument is weaker than this thread makes it sound.
Vitamin deficiency cascade with cardiovascular risk: after 6+ months of reduced food intake, I developed a subtle but important pattern: low B12 → elevated homocysteine → increased cardiovascular risk marker.
The connection: B12 is a cofactor for homocysteine metabolism. Without adequate B12, homocysteine accumulates. This is ironic — taking a CV-protective medication while developing a CV risk factor from reduced nutrition.
Solution: comprehensive vitamin supplementation and regular lab monitoring. Don't let the medication's benefits be undermined by nutritional deficiencies.
SarahChen_PharmD said:NNT calculation for cardiovascular risk clinical endpoints: NNT = 1/ARR (absolute risk reduction).
This is my experience too, for whatever a second data point is worth.