AHA 2023 | SELECT Trial: Semaglutide in Patients Without Diabetes

Given the obesity pandemic projected for the year 2035, it is imperative to address this disease as a priority, through well-known hygienic-dietary measures and the use of drugs that have shown promising results. Obesity has been identified as an independent cardiovascular risk factor, even after modifying risk factors associated with diabetes.

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Semaglutide, a GLP-1 agonist, has shown a significant reduction in major adverse cardiovascular events (MACE) in overweight/obese patients with diabetes. This type of agents affects a wide range of metabolic pathways related to glucose metabolism, energy homeostasis, and some triggers of inflammation, suggesting improvements in cardiovascular outcomes through multiple factors.

The SELECT study aimed to assess whether adding Semaglutide to standard treatment could outperform a placebo in reducing MACE in overweight or obese patients with pre-existing cardiovascular disease and without diabetes. It was a multicenter, randomized, superiority study conducted in 41 countries and included patients over 45 years old with a body mass index (BMI) of 27 or higher and a history of cardiovascular disease (myocardial infarction, stroke, or peripheral arterial disease).

Randomization was 1:1 between patients eligible for the administration of the target dose of subcutaneous Semaglutide 2.4 mg once a week and those who received a placebo. The primary efficacy endpoint was a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke.

Read also: AHA 2023 | Use of Apixaban for Stroke Prevention in Subclinical Atrial Fibrillation.

Of the 17,604 patients analyzed, 8803 were randomized to receive Semaglutide and 8801 to receive a placebo. The average age was 61.6 years, and 72% of the population was composed by men. The average BMI was 33 and the average glycated hemoglobin was 5.8. The primary endpoint occurred in 6.5% of patients receiving Semaglutide and 8% of the placebo group (hazard ratio [HR]: 0.80, 95% confidence interval [CI]: 0.72-0.90; P<0.001). Cardiovascular death occurred in 2.5% of the Semaglutide group and 3% of the placebo group (HR: 0.85, 95% CI: 0.71-1.01; p = 0.07), while the HR for the composite related to heart failure was 0.82 (95% CI: 0.71-0.96).

There was a 16.6% incidence of adverse effects leading to the discontinuation of Semaglutide, mainly related to gastrointestinal events (10%).

Dr. Omar Tupayachi

Dr. Omar Tupayachi.
Member of the Editorial Board of SOLACI.org.

Presented by Michael Lincoff in AHA 2023.

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