Semaglutide ‘A New Pathway’ to CVD Risk Reduction: SELECT

Semaglutide CVD risk reduction became a major topic of discussion after the final results of the SELECT trial showed that the anti-obesity drug semaglutide (Wegovy) reduced major cardiovascular events by around 20% compared with placebo. Researchers observed these benefits during approximately three years of follow-up in patients with overweight or obesity and established cardiovascular disease but without diabetes.

SELECT Trial Results

“This is a very exciting set of results. I think it is going to have a big impact on a large number of people,” said lead investigator A. Michael Lincoff, MD, vice chair for research in the Department of Cardiovascular Medicine at the Cleveland Clinic, Cleveland, Ohio, during an interview with theheart.org | Medscape Cardiology.

“From a scientific standpoint, these data show that we now have a new pathway or a new modifiable risk factor for cardiovascular disease that we can use in our patients who have overweight or obesity,” he added.

Study Design and Patient Population

The SELECT trial enrolled 17,604 patients with a history of cardiovascular disease and a BMI of 27 or above. The mean BMI was 33.

Researchers randomly assigned participants to receive either semaglutide or placebo.

Participants received semaglutide through a once-weekly subcutaneous injection. The dose gradually increased to 2.4 mg by week 16.

The mean baseline glycated hemoglobin level was 5.8%. In addition, 66.4% of patients met the criteria for prediabetes.

Weight Loss Findings

Patients lost a mean of 9.4% of body weight during the first two years with semaglutide. By comparison, patients in the placebo group lost 0.88% of body weight.

These findings further highlighted the metabolic effects observed during the SELECT trial.

Cardiovascular Outcomes

The primary cardiovascular endpoint included cardiovascular death, nonfatal myocardial infarction (MI), and nonfatal stroke.

Semaglutide significantly reduced the primary cardiovascular endpoint. Researchers reported a hazard ratio of 0.80 (95% CI, 0.72–0.90; P < .001).

The first confirmatory secondary endpoint examined death from cardiovascular causes. Researchers observed a 15% reduction (HR, 0.85; P = .07). However, the result did not reach statistical significance.

Because of the hierarchical trial design, investigators did not perform superiority testing for the remaining confirmatory secondary endpoints.

Secondary Endpoint Analysis

Furthermore, results showed reductions of around 20% for both the heart failure composite endpoint and all-cause mortality.

The confidence intervals did not cross 1.0. Researchers also observed directionally consistent effects across all supportive secondary endpoints.

The hazard ratio for the heart failure composite endpoint was 0.82 (95% CI, 0.71–0.96).

In addition, the hazard ratio for death from any cause was 0.81 (95% CI, 0.71–0.93).

Semaglutide reduced nonfatal myocardial infarction by 28%, with a hazard ratio of 0.72 (95% CI, 0.61–0.85).

Moreover, the treatment effects appeared similar across all prespecified subgroups.

Safety Profile

Adverse events led to treatment discontinuation in 16.6% of patients receiving semaglutide. Most of these events involved gastrointestinal (GI) effects.

By comparison, treatment discontinuation occurred in 8.2% of patients receiving placebo.

Presentation and Publication

Meanwhile, investigators presented the trial results at the 2023 American Heart Association (AHA) Scientific Sessions in Philadelphia.

The New England Journal of Medicine simultaneously published the findings online.

Conclusion

The SELECT trial demonstrated significant semaglutide CVD risk reduction in patients with overweight or obesity and established cardiovascular disease.

The findings support growing evidence that semaglutide may provide cardiovascular benefits beyond weight management while delivering consistent effects across multiple cardiovascular outcomes.

BESTBELL