{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T22:17:19Z","timestamp":1781821039906,"version":"3.54.5"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Glucagon-like peptide\u22121 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Four RCTs (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200919,663) showed semaglutide significantly reduced primary outcome risk (HR 0.83; 95% CI 0.76\u20130.91), nonfatal myocardial infarction (HR 0.79; 0.67\u20130.92), and revascularization (HR 0.71; 0.61\u20130.83), with a modest decrease in heart failure hospitalization (HR 0.85; 0.72\u20131.00). 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 \u201cmoderate\u201d for cardiovascular death, all-cause death, nonfatal stroke, unstable angina hospitalization, and \u201chigh\u201d for the remainder.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic Review Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/PROSPERO\/view\/CRD420251147337<\/jats:ext-link>\n                      , PROSPERO CRD420251147337.\n                    <\/jats:p>\n                  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