CureusJul 24, 2026

Cardiovascular benefits of semaglutide 2.4 mg in people with overweight or obesity: a review of current evidence

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Jul 25, 2026

Abstract

Semaglutide 2.4 mg is the first anti-obesity medication shown to have cardiovascular benefits in people with obesity without type 2 diabetes.

Obesity is closely linked to increased risks of cardiovascular disease and mortality.
The SELECT trial showed a reduction in major adverse cardiovascular events in individuals with obesity and established cardiovascular disease.
Evidence from heart failure studies indicates potential cardiovascular and functional benefits of semaglutide, separate from weight loss.
Real-world studies support the effectiveness of semaglutide in improving cardiovascular outcomes in obesity-related conditions.
Future regulatory approvals and clinical guidelines may influence the use of semaglutide in managing obesity-related cardiovascular risk.

Simplified

Obesity and cardiovascular (CV) disease (CVD) are tightly intertwined global epidemics, with excess adiposity now recognized as a major, modifiable driver of atherosclerotic events, heart failure, and mortality. Despite advances in cardiometabolic care, residual CV risk remains high in people with obesity, underscoring the need for therapies that both reduce body weight and directly modify CV risk. Semaglutide, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1RA), has emerged as a pivotal agent across the cardiometabolic spectrum, culminating in the SELECT trial, which demonstrated a reduction in three-point major adverse CV events (3P-MACE) in people with obesity and established CVD but without diabetes. Complementary evidence from heart failure with preserved ejection fraction (HFpEF) trials and real-world studies further supports a broad CV and functional benefit profile. This narrative review synthesizes data from randomized controlled trials (RCTs) and real-world evidence (RWE) on Wegovy® (semaglutide 2.4 mg, a recombinant DNA-derived GLP-1RA) in obesity with CVD, with a focus on SELECT, mediation analyses suggesting weight-independent CV effects, and outcomes in obesity-related HFpEF. We also discuss guideline positioning, regulatory milestones-including the 2025 Central Drugs Standard Control Organization (CDSCO) approval in India-and the evolving competitive landscape. Overall, semaglutide 2.4 mg represents the first and only anti-obesity medication with proven CV benefit in people with obesity without type 2 diabetes (T2D), with important implications for clinical practice and health policy.

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Competing interests

Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: Funding was supported by Novo Nordisk as independent publication support to Dr. Brij Teli. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

PubMed

Cardiovascular benefits of semaglutide 2.4 mg in people with overweight or obesity: a review of current evidence

Abstract

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