Primary results of SELECT, phase III cardiovascular outcomes trial of once-weekly semaglutide 2.4 mg (Wegovy) in adults with established cardiovascular disease and overweight or obesity without diabetes are presented at AHA meeting.- Novo Nordisk.

Previously reported top-line results showed semaglutide 2.4 mg 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). today’s 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 2.4 mg on body weight reduction. this suggests that weight loss alone may not fully explain the benefits of semaglutide 2.4 mg in reducing the risk of mace.></0.001).>

Every year almost 18 million people die from CVD which is the leading cause of disability and death worldwide. While cardiovascular mortality has decreased over the past two decades, obesity-related cardiovascular deaths have increased significantly. Obesity leads to cardiovascular morbidity and mortality and is associated with risk factors such as high blood pressure and inflammation.

“For the first time, we have evidence that semaglutide 2.4 mg 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).1 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).1 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 2.4 mg 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.

In the trial, semaglutide 2.4 mg appeared to have a safe and well-tolerated profile in line with previous semaglutide 2.4 mg trials.

Novo Nordisk has filed for a label update of Wegovy in the US and EU to include an indication for risk reduction of major adverse cardiovascular events in adults with a BMI of greater than 27 kg/m2 and established cardiovascular disease. A decision is expected in 2024. The FDA recently granted priority review for?the addition of the SELECT data?to the label for?Wegovy?in the US.

See-Lincoff A, Brown-Frandsen K, Colhoun H, et al. 2Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes". N Engl J Med. DOI: 10.1056/NEJMoa2307563.