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SELECT: Semaglutide reduces CV events in non-diabetic patients with overweight or obesity

Semaglutide 2.4mg (Wegovy) reduces cardiovascular events in patients with overweight or obesity and pre-existing cardiovascular disease who are not diabetic, according to the latest outcomes from the Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity (SELECT) trial presented at the American Heart Association (AHA) annual Scientific Sessions in Philadelphia and simultaneously published in the New England Journal of Medicine.

Previously reported top-line results showed semaglutide 2.4mg delivered a statistically significant 20% risk reduction in MACE over a period of up to five years versus placebo (HR: 0.80; 95% confidence interval: 0.72; 0.90, p<0.001). The latest findings showed that risk reductions in MACE were achieved regardless of age, gender, ethnicity and starting body mass index (BMI). The results also demonstrated that the beneficial effects in MACE risk reduction were evident soon after treatment initiation, suggesting an effect that is more rapid than what would be expected if the cardiovascular effects were entirely mediated with the effects of semaglutide 2.4mg on body weight reduction. This suggests that weight loss alone may not fully explain the benefits of semaglutide 2.4mg in reducing the risk of MACE.

Michael Lincoff

“For the first time, we have evidence that semaglutide 2.4mg improves cardiovascular outcomes in at-risk patients with BMI of 27 and above with established CVD, without diabetes,” said Dr Michael Lincoff, lead study author, vice chair for research in the Cleveland Clinic Department of Cardiovascular Medicine, and a paid consultant for Novo Nordisk. “The three-point MACE risk reduction observed in SELECT suggests the potential for a new option in obesity treatment, addressing some of the leading causes of preventable death worldwide.”

Analyses of the three components in MACE showed that the risk of non-fatal myocardial infarction or heart attack was reduced by 28% compared to placebo (HR: 0.72; 95% confidence interval: 0.61; 0.85), the risk of cardiovascular death was reduced by 15% (HR: 0.85; 95% confidence interval: 0.71; 1.01, not statistically significant over the length of the trial) and the risk of non-fatal stroke was reduced by 7% compared to placebo (HR: 0.93; 95% confidence interval: 0.74;1.15, not statistically significant over the length of the trial). In addition, beneficial effects were seen consistently across measured cardiovascular endpoints.

The confirmatory secondary endpoints showed that the risk of composite heart failure events, comprising cardiovascular death, urgent heart failure visits and hospitalisations, was reduced by 18% compared to placebo (HR: 0.82; 95% confidence interval: 0.71; 0.96) and the risk of death from any cause was reduced by 19% compared to placebo (HR: 0.81; 95% confidence interval: 0.71; 0.93). As the result on cardiovascular death was not statistically significant over the length of the trial, the remaining secondary confirmatory endpoints were not tested for superiority due to hierarchical testing.

The supportive secondary endpoints also showed beneficial effects of semaglutide 2.4mg on other cardiovascular risk factors, including lowering blood pressure, cholesterol and blood sugar levels. While the trial was not designed as a weight loss trial, participants in the trial who received semaglutide still lost an average of 9.4% of total body weight which was sustained throughout the trial.

SELECT was a randomised, double-blind, parallel-group, placebo-controlled trial designed to evaluate the efficacy of semaglutide 2.4 mg versus placebo as an adjunct to standard of care for reducing the risk of MACE in people with established CVD with overweight or obesity with no prior history of diabetes.

People included in the trial were aged ≥45 years with a BMI ≥27 kg/m2. Baseline demographics by age group show that 24% were aged 45-54, 38% aged 55-64, 30% aged 65-74 and 8% aged 75 years plus. By race or ethnicity, 84% of trial participants were white, 10% Hispanic or Latino, 8% Asian, 4% black and 3% other. The split between male and female participants was 72% and 28% respectively.

The trial enrolled 17,604 adults and has been conducted in 41 countries at more than 800 investigator sites. SELECT was initiated in 2018 and is the largest trial Novo Nordisk has ever conducted.

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