SELECT trial (revision 8)
Old revision·21:29, 2 Nov 2024·CategoryBot
| SELECT trial | |
|---|---|
| Drug | Semaglutide 2.4 mg weekly |
| Population | Established CVD, BMI ≥27, no diabetes |
| Participants | 17,604 |
| Primary result | MACE HR 0.80 (95% CI 0.72–0.90) |
| Topic infobox · conventions | |
SELECT was a randomised, double-blind, placebo-controlled cardiovascular outcome trial of weekly semaglutide 2.4 mg in 17,604 adults with established cardiovascular disease and a body-mass index of 27 or above, and without diabetes.[1]
The primary composite outcome — cardiovascular death, non-fatal myocardial infarction or non-fatal stroke — occurred in 6.5% of the semaglutide group and 8.0% of the placebo group over a mean follow-up of 39.8 months, a hazard ratio of 0.80 (95% CI 0.72–0.90).[1]
Its significance is that it studied an outcome rather than an intermediate endpoint, in a population without diabetes. Previous cardiovascular evidence for this class came from trials in type 2 diabetes, where the benefit could plausibly be attributed to glycaemic effects.[2]
Design
[edit]Participants were 45 or older with established cardiovascular disease — prior myocardial infarction, prior stroke, or symptomatic peripheral arterial disease — and overweight or obesity, and were excluded if they had diabetes. Both groups continued standard cardiovascular care.[1]
This is an important design feature: the trial tested semaglutide added to background therapy including statins and antiplatelet agents in a majority of participants, so the observed effect is incremental to contemporary secondary prevention rather than a comparison against nothing.
Mean weight reduction on active treatment was about 9.4%, less than the 14.9% seen in STEP 1 — a reminder that trial populations differ and that an effect size does not transfer between them.[3]
Results and their interpretation
[edit]| Endpoint | Semaglutide | Placebo | Effect |
|---|---|---|---|
| Primary composite | 6.5% | 8.0% | HR 0.80 (0.72–0.90) |
| Cardiovascular death | 2.5% | 3.0% | Directionally consistent |
| Non-fatal myocardial infarction | 2.7% | 3.7% | Directionally consistent |
| Discontinuation for adverse events | 16.6% | 8.2% | Mostly gastrointestinal |
Separation of the event curves began early, within the first months, before the majority of weight loss had occurred. Whether the benefit is mediated by weight reduction, by direct vascular effects, by improvements in blood pressure and inflammatory markers, or by some combination is not established by the trial.[1]
References
- ^ a b c d Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. "Semaglutide and cardiovascular outcomes in obesity without diabetes." New England Journal of Medicine 389(24):2221–2232 (2023). DOI:10.1056/NEJMoa2307563. PMID 37952131.
- ^ Marso SP, Bain SC, Consoli A, et al. "Semaglutide and cardiovascular outcomes in patients with type 2 diabetes." New England Journal of Medicine 375(19):1834–1844 (2016). PMID 27633186.
- ^ Wilding JPH, Batterham RL, Calanna S, et al. "Once-weekly semaglutide in adults with overweight or obesity." New England Journal of Medicine 384(11):989–1002 (2021). PMID 33567185.