{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T04:38:49Z","timestamp":1792471129137,"version":"4.5.0"},"reference-count":34,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To assess the effect of all the approved classes of medications for type 2 diabetes on Major Adverse Cardiovascular events (MACE) and all\u2010cause mortality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a pairwise and network meta\u2010analysis, including randomised controlled trials with a duration of at least 40\u2009weeks, comparing medications versus placebo or an active comparator, in which MACE and deaths were adjudicated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We included 93 studies. In pairwise meta\u2010analyses, versus all comparators, GLP\u20101 receptor agonists (GLP1RA), SGLT\u20102 inhibitors (SGLT2i), metformin and pioglitazone were associated with a significant reduction of MACE and sulfonylureas with increased MACE. Furthermore, tirzepatide, SGLT2i and GLP1RA were associated with a significantly reduced all\u2010cause mortality. In the principal (frequentist) network meta\u2010analysis, metformin (OR 0.69, 95% CI 0.53\u20130.89), SGLT2i (0.82, 0.75\u20130.90), GLP1RA (0.87, 0.83\u20130.92) and tirzepatide (0.82, 0.72\u20130.93) were associated with a significant reduction of MACE versus placebo; no effect was observed for insulin, DPP4 inhibitors (DPP4i) or sulfonylureas. Tirzepatide (0.72, 0.64\u20130.82), SGLT2i (0.85, 0.80\u20130.91) and GLP1RA (0.85, 0.80\u20130.91) were associated with a significantly reduced mortality versus placebo; no effect was detected for other drugs. The sensitivity (Bayesian) analysis did not confirm the significance of results for pioglitazone on MACE. The certainty of evidence was moderate\u2010to\u2010high for GLP1RA, SGLT2i, Tirzepatide, DPP4i; low for metformin; low\u2010to\u2010moderate for other drugs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>SGLT2i, GLP1RA, tirzepatide and (with lower quality of evidence) pioglitazone and metformin are associated with a reduced incidence of cardiovascular events; tirzepatide, SGLT2i and GLP1RA are also associated with a reduced all\u2010cause mortality.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.71128","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:57:56Z","timestamp":1785416276000},"page":"9403-9411","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effect of Medications for Type 2 Diabetes on Cardiovascular Events and Mortality: A Comprehensive Pairwise and Network Meta\u2010Analysis"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6695-3213","authenticated-orcid":false,"given":"Giovanni Antonio","family":"Silverii","sequence":"first","affiliation":[{"name":"Diabetology Unit Careggi Hospital  Florence Italy"},{"name":"University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4516-8427","authenticated-orcid":false,"given":"Valerio","family":"Velardi","sequence":"additional","affiliation":[{"name":"Department of Medical Surgical and Health Sciences University of Trieste  Trieste Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Marinelli","sequence":"additional","affiliation":[{"name":"Diabetology Unit Careggi Hospital  Florence Italy"},{"name":"University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonino","family":"Lax","sequence":"additional","affiliation":[{"name":"Diabetology Unit Careggi Hospital  Florence Italy"},{"name":"University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9349-828X","authenticated-orcid":false,"given":"Matteo","family":"Monami","sequence":"additional","affiliation":[{"name":"Diabetology Unit Careggi Hospital  Florence Italy"},{"name":"University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9759-9408","authenticated-orcid":false,"given":"Edoardo","family":"Mannucci","sequence":"additional","affiliation":[{"name":"Diabetology Unit Careggi Hospital  Florence Italy"},{"name":"University of Florence  Florence 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