Successful results for semaglutide in the highly anticipated SELECT trial 

Semaglutide successfully reduced adverse cardiovascular outcomes in patients with cardiovascular disease (CVD) who are overweight but without diabetes. No unexpected safety issues emerged with semaglutide in this population. 

The randomised, double-blind, placebo-controlled, phase 3 SELECT trial (NCT03574597) assessed the safety and efficacy of the GLP-1 receptor agonist semaglutide, added to standard-of-care, in patients with pre-existing CVD and overweight or obesity but without diabetes [1]. The 17,604 participants were randomised 1:1 to 2.4 mg semaglutide (subcutaneously administered once weekly) or a placebo. Of note, the dosing of semaglutide was titrated, starting at a dose of 0.24 mg and increasing to the anticipated dose of 2.4 mg at week 16. The primary outcome was a composite of cardiovascular death, non-fatal myocardial infarction (MI), or non-fatal stroke, measured at week 48.

“Semaglutide met its primary endpoint in this trial,” expressed Dr Michael Lincoff (Cleveland Clinic, OH, USA) (see Figure). The event rate was 8.0% in the placebo arm and 6.5% in the semaglutide arm, with a corresponding hazard ratio of 0.80 (95% CI 0.72–0.90; P<0.001). Further, the primary outcome result was consistent across pre-defined subgroups.

Figure: Primary cardiovascular composite endpoint at 48 weeks [1]



The first confirmatory secondary endpoint of cardiovascular death was numerically but not significantly in favour of the semaglutide arm (HR 0.85; 95% CI 0.71–1.01; P=0.065). The second and third confirmatory secondary endpoints, which were a heart failure composite and death from any cause, showed benefits for participants randomised to semaglutide over those randomised to placebo (HR 0.82; 95% CI 0.71–0.96; HR 0.81; 95% CI 0.71–0.93).

Finally, no unexpected safety issues were encountered. The rate of gastrointestinal adverse events was higher in the semaglutide arm than in the placebo arm (10.0% vs 2.0%; P<0.001). However, the rates of serious gastrointestinal events were similar between the groups.

1. Lincoff AM, et al. Semaglutide and cardiovascular outcomes in patients with overweight or obesity and cardiovascular disease who do not have diabetes: the SELECT trial. LB01, AHA Scientific Sessions 2023, 11–13 November, Philadelphia, USA.

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Posted on 29 January, 202429 January, 2024