Source of SELECT trial

{{Infobox concept | name = SELECT trial | subtitle = Cardiovascular outcome trial | Drug = [[Semaglutide|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) }} '''SELECT''' was a randomised, double-blind, placebo-controlled cardiovascular outcome trial of weekly [[Semaglutide|semaglutide]] 2.4 mg in 17,604 adults with established cardiovascular disease and a body-mass index of 27 or above, and without diabetes.{{r|lincoff2023}} 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).{{r|lincoff2023}} 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.{{r|marso2016s}} == Design == 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.{{r|lincoff2023}} 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 trial programme|STEP 1]] — a reminder that trial populations differ and that an effect size does not transfer between them.{{r|wilding2021}} == Results and their interpretation == | 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.{{r|lincoff2023}} The [[Number needed to treat|number needed to treat]] can be computed from the absolute risk difference of 1.5 percentage points over roughly 3.3 years, giving approximately 67 over that period. Absolute rather than relative figures are what allow benefit and harm to be compared on the same scale.{{r|nnt_ref}} == What it changed == SELECT supported a cardiovascular risk-reduction indication for semaglutide 2.4 mg in the studied population, distinct from the weight-management indication, and it did so in a population without diabetes.{{r|lincoff2023}} It does not establish benefit in primary prevention, in people without overweight or obesity, or for other members of the [[GLP-1 receptor agonist|class]]. Within the class, the outcome trials have not all been positive — the exenatide trial was neutral and the lixisenatide trial was neutral — so a class claim is not supported. See [[Exenatide]].{{r|marso2016s}} The 16.6% discontinuation for adverse events against 8.2% on placebo is the other side of the result and belongs in any summary of it. See [[Adverse effects of GLP-1 receptor agonists]].{{r|lincoff2023}} == References == {{reflist}} <ref name="lincoff2023">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.</ref> <ref name="marso2016s">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.</ref> <ref name="wilding2021">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.</ref> <ref name="nnt_ref">Laupacis A, Sackett DL, Roberts RS. "An assessment of clinically useful measures of the consequences of treatment." ''New England Journal of Medicine'' 318(26):1728–1733 (1988). PMID 3374545.</ref> == External links == * [https://clinicaltrials.gov/study/NCT03574597 SELECT — NCT03574597] — Registry record. == See also == * [[Semaglutide]] * [[STEP trial programme]] * [[LEADER trial]] * [[FLOW trial]] * [[Number needed to treat]] * [[GLP-1 receptor agonist]] {{DEFAULTSORT:SELECT trial}} [[Category:Cardiovascular outcome trials]] [[Category:Clinical evidence]] [[Category:Obesity trials]]