SELECT trial (revision 6)

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]

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.