{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:58:44Z","timestamp":1790657924470,"version":"4.1.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"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>While injectable GLP-1 receptor agonists like semaglutide have demonstrated clear cardiovascular benefits in type 2 diabetes mellitus (T2DM), the role of oral incretin-based therapies, including oral semaglutide and DPP-4 inhibitors\u2014remains less well defined. Comprehensive evaluation of their cardiovascular efficacy is warranted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Research question<\/jats:title>\n                    <jats:p>What are the cardiovascular outcomes associated with oral incretin-based therapies, specifically oral semaglutide and DPP-4 inhibitors, in patients with T2DM compared to placebo or standard care.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We searched electronic databases for randomized controlled trials (RCTs). Meta-analysis was conducted in R version 4.4.3 using the \u201cmeta\u201d and \u201cmetasens\u201d packages. Statistical analysis was performed using R software and RStudio (version 4.4.2). We calculated pooled estimates using risk ratios (RR) with 95% confidence intervals (CIs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 9 studies comprising 67,679 patients were included, of which two evaluated oral semaglutide and the remaining seven assessed DPP-4 inhibitors. There was no significant reduction in all-cause mortality (RR 0.97, 95% CI 0.90\u20131.04,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.35) or cardiovascular death (RR 0.98, 95% CI 0.91\u20131.05,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.48). Major adverse cardiovascular events (MACE) showed a non-significant reduction overall (RR 0.95, 95% CI 0.91\u20131.00,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.06), with oral semaglutide demonstrating a significant benefit (RR 0.86, 95% CI 0.78\u20130.95,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.003). Non-fatal myocardial infarction (MI) (RR 0.98, 95% CI 0.88\u20131.09) and non-fatal stroke (RR 0.93, 95% CI 0.83\u20131.03) were not significantly affected. Hospitalizations due to heart failure (RR 0.98, 95% CI 0.84\u20131.13) and unstable angina (RR 1.00, 95% CI 0.87\u20131.15) remained unchanged. Coronary revascularization was slightly reduced with oral semaglutide (RR 0.76, 95% CI 0.64\u20130.91). Adverse events leading to discontinuation were higher with oral semaglutide (RR 1.51, 95% CI 1.15\u20131.98), while serious adverse events were significantly reduced (RR 0.96, 95% CI 0.94\u20130.99,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.003). Sensitivity analyses were conducted due to significant heterogeneity in key outcomes. While omitting certain studies reduced heterogeneity, the overall results remained consistent.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Oral incretin-based therapies were not associated with significant reductions in all-cause mortality, cardiovascular death, or MACE overall, though oral semaglutide showed a significant MACE benefit and reduced coronary revascularization on subgroup analysis. Non-fatal MI, fatal or non-fatal MI, non-fatal stroke, fatal or non-fatal stroke and hospitalization due to heart failure or unstable angina were unaffected, and oral semaglutide carried a higher risk of treatment discontinuation. These findings suggest no clear class-wide cardiovascular benefit of oral incretins, with signals specific to oral semaglutide warranting confirmation in dedicated trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic Review Registration<\/jats:title>\n                    <jats:p>PROSPERO CRD420251113835.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcvm.2026.1884895","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:38:58Z","timestamp":1790656738000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cardiovascular outcomes of oral incretin-based drugs in type 2 diabetes: a GRADE-assessed meta-analysis of 67,679 patients"],"prefix":"10.3389","volume":"13","author":[{"given":"Muhammad Faizan","family":"Ali","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, HCA Healthcare 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Fawzi","family":"Hemida","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Alexandria Main University Hospital","place":["Alexandria, Egypt"]},{"name":"Department of Internal Medicine, University of Vermont , Burlington","place":["VT, United States"]},{"name":"Department of Cardiovascular Medicine, American Society for Inclusion, Diversity, and Equity in Healthcare (ASIDE) , Lewes","place":["DE, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1677\/JOE-09-0260","article-title":"Current views on type 2 diabetes","volume":"204","author":"Lin","year":"2009","journal-title":"J Endocrinol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"109119","DOI":"10.1016\/j.diabres.2021.109119","article-title":"IDF Diabetes atlas: global, regional and country-level diabetes prevalence estimates 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