Insights into semaglutide cardiovascular research: Mechanisms, trials, and frontiers.

Cardiovascular disease (CVD) remains the leading cause of global mortality, with pathophysiological alterations such as heart failure with preserved ejection fraction, diabetic cardiomyopathy, and atherosclerotic cardiomyopathy representing major risk factors. Semaglutide, a novel long-acting glucagon-like peptide-1 receptor agonist, has demonstrated substantial efficacy in glycemic control and weight reduction. Since 2016, accumulating evidence has highlighted its promising cardiovascular benefits, establishing semaglutide as a strong therapeutic candidate for CVD. This review synthesizes evidence since 2016 to elucidate semaglutide's cardiovascular outcomes, underlying mechanisms, and emerging frontiers, employing bibliometric analytical approaches such as burst detection mapping and cluster timeline analysis of references and keywords. Research on semaglutide in CVD has advanced rapidly, with mechanistic insights including improvements in insulin resistance, anti-inflammatory activity, and anti-atherosclerotic effects, as well as novel associations with ferroptosis inhibition. Clinical evidence across diverse patient subgroups indicates that future implementation will require precision-based regimen design. Moreover, although oral semaglutide alleviates injection-related discomfort, its gastrointestinal tolerability remains a concern. Furthermore, the potential reduction in lean mass requires further validation. Overall, this review aims to broaden the clinical application of semaglutide and highlight novel therapeutic avenues for patients with cardiovascular disease.