{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T03:51:17Z","timestamp":1777866677221,"version":"3.51.4"},"reference-count":23,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,12,27]],"date-time":"2023-12-27T00:00:00Z","timestamp":1703635200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To explore the risk of major adverse cardiovascular events (MACE) associated with exposure to bexagliflozin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The analysis included 4090 participants with type 2 diabetes (T2D) enrolled in nine phase 2 and 3 double\u2010blind randomized controlled trials. All potential MACE were adjudicated by a blinded committee. The primary endpoint for the meta\u2010analysis was the hazard ratio (HR) for the time to first occurrence of non\u2010fatal stroke, non\u2010fatal myocardial infarction (MI), cardiovascular (CV) death or hospitalization for unstable angina (MACE+), tested for non\u2010inferiority to a ratio of 1.8. The secondary endpoints were time to first occurrence of (i) non\u2010fatal stroke, non\u2010fatal MI or CV death (MACE), tested for non\u2010inferiority to a ratio of 1.3; and (ii) CV death or hospitalization for heart failure, tested for superiority.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The HR for the primary endpoint of MACE+ was 0.80 (95% confidence interval [CI] 0.58, 1.09), which fulfilled the non\u2010inferiority objective with a\n                      <jats:italic>P<\/jats:italic>\n                      value of less than 0.0001. Non\u2010inferiority for the first key secondary endpoint of MACE was also shown (HR\u2009=\u20090.82; 95% CI 0.59, 1.13;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.0023). Superiority for time to CV death or first hospitalization for heart failure was not shown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Bexagliflozin did not increase the risk of MACE in participants with T2D when compared with placebo or active control. Both the preapproval and postapproval thresholds for CV safety were met and bexagliflozin has been approved by the US Food and Drug Administration.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.15394","type":"journal-article","created":{"date-parts":[[2023,12,27]],"date-time":"2023-12-27T23:44:40Z","timestamp":1703720680000},"page":"971-979","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["<scp>Meta\u2010analysis<\/scp>\n                    of risk of major adverse cardiovascular events in adults with type 2 diabetes treated with bexagliflozin"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6317-3975","authenticated-orcid":false,"given":"John J. V.","family":"McMurray","sequence":"first","affiliation":[{"name":"BHF Glasgow Cardiovascular Research Centre University of Glasgow  Glasgow UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott D.","family":"Solomon","sequence":"additional","affiliation":[{"name":"Cardiovascular Division Brigham and Women's Hospital  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. Paul","family":"Lock","sequence":"additional","affiliation":[{"name":"Diabetes Center of Excellence, Department of Medicine University of Massachusetts  Worcester Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph M.","family":"Massaro","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Boston University School of Public Health  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Navitas Life Sciences  Princeton New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjiong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Hopkins Consulting LLC  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hicham","family":"Skali","sequence":"additional","affiliation":[{"name":"Cardiovascular Division Brigham and Women's Hospital  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eldrin F.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine Stanford Health Care  Palo Alto California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5254-9244","authenticated-orcid":false,"given":"Mason W.","family":"Freeman","sequence":"additional","affiliation":[{"name":"Translational Medicine Group, Center for Computational and Integrative Biology Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2490-8024","authenticated-orcid":false,"given":"Yuan\u2010Di C.","family":"Halvorsen","sequence":"additional","affiliation":[{"name":"Translational Medicine Group, Center for Computational and Integrative Biology Massachusetts General Hospital  Boston Massachusetts 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