{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T23:17:04Z","timestamp":1792279024156,"version":"4.4.0"},"reference-count":70,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T00:00:00Z","timestamp":1747353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministero della Salute"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Patients with active cancer and cancer survivors are at a markedly increased risk for developing cardiovascular comorbidities, including heart failure, coronary artery disease, and renal dysfunction, which are often compounded by the cardiotoxic effects of cancer therapies. This heightened cardiovascular vulnerability underscores the urgent need for effective, safe, and evidence-based cardioprotective strategies to reduce both cardiovascular morbidity and mortality. Sodium-glucose cotransporter 2 inhibitors (SGLT2is), a class of drugs originally developed for the treatment of type 2 diabetes, have demonstrated significant cardiovascular and renal benefits in high-risk populations, independent of glycemic control. Among the currently available SGLT2i, such as empagliflozin, canagliflozin, dapagliflozin, and sotagliflozin, there is growing evidence supporting their role in reducing major adverse cardiovascular events (MACEs), hospitalization for heart failure, and the progression of chronic kidney disease. Recent preclinical and clinical data suggest that SGLT2is exert cardioprotective effects through multiple mechanisms, including the modulation of inflammasome activity, specifically by reducing NLRP3 inflammasome activation and MyD88-dependent signaling, which are critical drivers of cardiac inflammation and fibrosis. Moreover, SGLT2is have been shown to enhance mitochondrial viability in cardiac cells, promoting improved cellular energy metabolism and function, thus mitigating cardiotoxicity. This narrative review critically evaluates the emerging evidence on the cardiorenal protective mechanisms of SGLT2is, with a particular focus on their potential role in cardio-oncology. We explore the common pathophysiological pathways between cardiovascular dysfunction and cancer, the molecular rationale for the use of SGLT2is in cancer patients, and the potential benefits in both primary and secondary prevention of cardiovascular toxicity related to oncological treatments. The aim is to propose a therapeutic paradigm utilizing SGLT2is to reduce cardiovascular mortality, MACE, and the burden of cardiotoxicity in high-risk oncology patients, fostering an integrated approach to cardio-oncology care.<\/jats:p>","DOI":"10.3390\/ijms26104780","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T08:32:29Z","timestamp":1747384349000},"page":"4780","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["SGLT2 Inhibitors in Cancer Patients: A Comprehensive Review of Clinical, Biochemical, and Therapeutic Implications in Cardio-Oncology"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3130-0079","authenticated-orcid":false,"given":"Alessandra","family":"Greco","sequence":"first","affiliation":[{"name":"Cardiology Division, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Laura","family":"Canale","sequence":"additional","affiliation":[{"name":"Cardiology, Versilia Hospital, Azienda USL Toscana Nord-Ovest, 55041 Lido di Camaiore, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4557-5401","authenticated-orcid":false,"given":"Vincenzo","family":"Quagliariello","sequence":"additional","affiliation":[{"name":"Cardiology Division, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, 80145 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Oliva","sequence":"additional","affiliation":[{"name":"UOSD Cardiologia di interesse oncologico, IRCCS Istituto Tumori \u201cGiovanni Paolo II\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0315-3304","authenticated-orcid":false,"given":"Andrea","family":"Tedeschi","sequence":"additional","affiliation":[{"name":"Cardiology, \u201cGuglielmo da Saliceto\u201d Hospital, 29121 Piacenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6331-6908","authenticated-orcid":false,"given":"Alessandro","family":"Inno","sequence":"additional","affiliation":[{"name":"Medical Oncology, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar di Valpolicella, 37024 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1873-1891","authenticated-orcid":false,"given":"Marzia","family":"De Biasio","sequence":"additional","affiliation":[{"name":"Cardiology, Azienda Sanitaria Universitaria Friuli Centrale, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0689-0695","authenticated-orcid":false,"given":"Irma","family":"Bisceglia","sequence":"additional","affiliation":[{"name":"Servizi Cardiologici Integrati, Dipartimento di Scienze Cardio-Toraco-Vascolari, Azienda Ospedaliera San Camillo Forlanini, 00148 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2580-0963","authenticated-orcid":false,"given":"Luigi","family":"Tarantini","sequence":"additional","affiliation":[{"name":"S.O.C. Cardiologia Ospedaliera, Presidio Ospedaliero Arcispedale Santa Maria Nuova, Azienda USL di Reggio Emilia-IRCCS, 42100 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3704-0092","authenticated-orcid":false,"given":"Nicola","family":"Maurea","sequence":"additional","affiliation":[{"name":"Cardiology Division, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, 80145 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8417-7783","authenticated-orcid":false,"given":"Alessandro","family":"Navazio","sequence":"additional","affiliation":[{"name":"S.O.C. Cardiologia Ospedaliera, Presidio Ospedaliero Arcispedale Santa Maria Nuova, Azienda USL di Reggio Emilia-IRCCS, 42100 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Corda","sequence":"additional","affiliation":[{"name":"S.C. Cardiologia, Azienda di Rilievo Nazionale e Alta Specializzazione \u201cG. Brotzu\u201d, 09047 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attilio","family":"Iacovoni","sequence":"additional","affiliation":[{"name":"SSD Chirurgia dei Trapianti e del Trattamento Chirurgico dello Scompenso, Dipartimento Cardiovascolare, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7187-2234","authenticated-orcid":false,"given":"Furio","family":"Colivicchi","sequence":"additional","affiliation":[{"name":"UOC Cardiologia Clinica e Riabilitativa, Presidio Ospedaliero San Filippo Neri\u2014ASL Roma 1, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9347-8884","authenticated-orcid":false,"given":"Massimo","family":"Grimaldi","sequence":"additional","affiliation":[{"name":"UOC Cardiologia-UTIC, Ospedale Miulli, Acquaviva delle Fonti (BA), 70021 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Oliva","sequence":"additional","affiliation":[{"name":"Cardiologia 1-Emodinamica, Dipartimento Cardiotoracovascolare \u201cA. De Gasperis\u201d, ASST Grande Ospedale Metropolitano Niguarda, 20162 Milan, Italy"},{"name":"Presidente ANMCO\u2014Associazione Nazionale Medici Cardiologi Ospedalieri, 50121 Florence, Italy"},{"name":"Consigliere Delegato per la Ricerca Fondazione per il Tuo Cuore-Heart Care Foundation, 50121 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.1016\/j.jacc.2023.04.034","article-title":"Effect of SGLT2 Inhibitors on Cardiovascular Outcomes Across Various Patient Populations","volume":"81","author":"Usman","year":"2023","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Abdelrahman, A.M., Awad, A.S., and Abdel-Rahman, E.M. (2024). Sodium-Glucose Co-Transporter 2 Inhibitors: Mechanism of Action and Efficacy in Non-Diabetic Kidney Disease from Bench to Bed-Side. J. 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