Successful results for semaglutide in highly anticipated SELECT trial

Semaglutide successfully reduced adverse cardiovascular outcomes in patients with pre-existing cardiovascular disease (CVD) and overweight, but without diabetes, showing that overweight is a modifiable risk factor for CVD. 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 built up, 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 CV death, non-fatal myocardial infarction (MI), or non-fatal stroke, measured at week 48. Dr Michael Lincoff (Cleveland Clinic, OH, USA) presented the primary results.

“Semaglutide met its primary endpoint in this trial,” expressed Dr Lincoff. 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.

The first confirmatory secondary endpoint of CV 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.

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   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, 10–12 November, Philadelphia, USA.

 

Medical writing support was provided by Robert van den Heuvel.
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Posted on 15 November, 202315 November, 2023