Effects of subcutaneous or oral semaglutide on cardiovascular outcomes in patients with type 2 diabetes mellitus: a meta-analysis of randomized controlled trials
Year: 2025
Type: review
Study designs: Systematic Review, Meta-Analysis
Abstract: Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), such as semaglutide, reduce cardiovascular risk in type 2 diabetes mellitus (T2DM), but the consistency between oral and subcutaneous formulations remains unclear. Methods: This meta-analysis was registered prospectively in PROSPERO (CRD 420251147337). A systematic search of PubMed, Embase, Cochrane Library, and Web of Science identified randomized controlled trials (RCTs) on semaglutide and cardiovascular outcomes. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using fixed-/random-effects models, with sensitivity, subgroup, and GRADE assessments. Results: = 19,663) showed semaglutide significantly reduced primary outcome risk (HR 0.83; 95% CI 0.76-0.91), nonfatal myocardial infarction (HR 0.79; 0.67-0.92), and revascularization (HR 0.71; 0.61-0.83), with a modest decrease in heart failure hospitalization (HR 0.85; 0.72-1.00). No significant effects were seen for cardiovascular death, all-cause death, nonfatal stroke, or unstable angina hospitalization. Subgroup analyses confirmed no efficacy differences between formulations. Evidence quality was "moderate" for cardiovascular death, all-cause death, nonfatal stroke, unstable angina hospitalization, and "high" for the remainder. Conclusions: Semaglutide lowers cardiovascular risk in T2DM, primarily improving major adverse cardiovascular events, nonfatal myocardial infarction, and revascularization, with oral and subcutaneous forms demonstrating consistent efficacy. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251147337, PROSPERO CRD420251147337.
Authors: Sihua Tan, Yangguang Yin, Juexiu Lu
Institution: Chongqing Medical and Pharmaceutical College
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W4417311565