Recent breakthroughs in medical research have highlighted the dual benefits of certain weight-loss medications, particularly semaglutide, in addressing obesity and its associated cardiovascular risks. Emerging data suggests that semaglutide may not only aid in weight reduction but also significantly reduce the incidence of major adverse cardiac events (MACE) in individuals with cardiovascular disease (CVD), even in the absence of diabetes.

The SELECT Trial: A Landmark Study

The SELECT trial, a large-scale, double-blinded, randomized study, enrolled over 17,600 participants aged 45 and older, all with a BMI of at least 27 kg/m² and established cardiovascular disease. Approximately 25% of participants had heart failure at baseline. Participants were divided to receive either semaglutide 2.4 mg weekly or a placebo over 34 months, with follow-up lasting an average of 39 months.

Key findings include:

• 28% reduction in MACE among participants with heart failure.

• Decreased risk of cardiovascular death by 24% and all-cause mortality by 19%.

• Similar efficacy in heart failure subtypes: 35% reduction in MACE for heart failure with reduced ejection fraction (HFrEF) and 31% for heart failure with preserved ejection fraction (HFpEF).

• Consistent benefits across age, gender, BMI, and heart failure severity.

How Semaglutide Works

Semaglutide is a glucagon-like peptide 1 (GLP-1) receptor agonist. It mimics the GLP-1 hormone, promoting insulin secretion, lowering blood sugar, and influencing brain areas controlling appetite. These mechanisms contribute to weight loss and cardiovascular benefits, likely through reduced inflammation, improved lipid profiles, and lowered blood pressure.

Beyond Weight Loss: Cardiac Benefits

The SELECT trial findings align with other studies emphasizing GLP-1 receptor agonists’ potential to improve cardiovascular health. For example:

• In heart failure patients, semaglutide improved symptoms and exercise capacity.

• Another GLP-1 agonist, tirzepatide, demonstrated reductions in left ventricular mass and epicardial adipose tissue, suggesting structural cardiac improvements.

Semaglutide’s benefits were also evident in patients with a history of coronary artery bypass grafting (CABG). In these individuals, semaglutide reduced MACE more effectively than in non-CABG patients, showcasing its utility in high-risk populations.

Safety and Tolerability

While generally safe, semaglutide may cause gastrointestinal side effects such as nausea, which often resolve with dosage adjustments. Its cardiovascular and metabolic benefits far outweigh these temporary issues, particularly for patients with obesity and established CVD.

Implications for Clinical Practice

These findings redefine semaglutide from a diabetes and weight-loss drug to a transformative therapy for cardiovascular disease prevention. With obesity and heart disease prevalence rising globally, semaglutide offers hope for a broader patient demographic, including those without diabetes.

Future Directions

Ongoing research focuses on the intricate relationship between obesity, inflammation, and cardiovascular health. Investigators aim to refine GLP-1 receptor agonist therapies, optimizing their application in diverse patient populations.

Conclusion

Semaglutide represents a paradigm shift in managing obesity and cardiovascular disease. As clinicians and researchers continue to explore its full potential, this drug underscores the growing recognition of the interplay between metabolic health and heart disease.

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4. González-Vargas, Javier, et al.
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