{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T02:20:03Z","timestamp":1791339603818,"version":"4.3.1"},"reference-count":153,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"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. Pharmacol."],"abstract":"<jats:p>Metformin, a cornerstone therapy for type 2 diabetes mellitus, has emerged as a promising cardioprotective agent with effects that extend well beyond glycemic control. This review synthesizes current evidence on the molecular and cellular mechanisms underlying metformin\u2019s glycemic control and cardiovascular benefits, highlighting both AMPK-dependent and AMPK-independent pathways. We examine its modulation of mitochondrial function, oxidative stress, inflammation, autophagy, and apoptosis across major cardiac conditions, including ischemia\/reperfusion injury, heart failure, diabetic cardiomyopathy, and anthracycline-induced cardiotoxicity. By integrating evidence from both preclinical and clinical studies, we evaluate the translational potential of metformin\u2019s pleiotropic actions across specific cardiac pathologies and outline key directions for future research and therapeutic innovation. Together, these insights highlight metformin\u2019s promise in reshaping cardiovascular care beyond its traditional role in diabetes management.<\/jats:p>","DOI":"10.3389\/fphar.2026.1681783","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T09:03:41Z","timestamp":1770023021000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Repurposing metformin for cardioprotection: mechanisms and therapeutic potential across cardiovascular pathologies"],"prefix":"10.3389","volume":"17","author":[{"given":"Julia","family":"Khinchin","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, New York Institute of Technology, College of Osteopathic Medicine","place":["Old Westbury, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ani","family":"Rakoubian","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, New York Institute of Technology, College of Osteopathic Medicine","place":["Old Westbury, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Romano","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, New York Institute of Technology, College of Osteopathic Medicine","place":["Old Westbury, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Ryan","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, New York Institute of Technology, College of Osteopathic Medicine","place":["Old Westbury, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnathan","family":"Yarbro","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, New York Institute of Technology, College of Osteopathic Medicine","place":["Old Westbury, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, New York Institute of Technology, College of Osteopathic Medicine","place":["Old Westbury, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiangrong","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, New York Institute of Technology, College of Osteopathic Medicine","place":["Old Westbury, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,2]]},"reference":[{"key":"B2","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1161\/CIRCHEARTFAILURE.110.952556","article-title":"Metformin use and mortality in ambulatory patients with diabetes and heart failure","volume":"4","author":"Aguilar","year":"2011","journal-title":"Circ. 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