{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T18:28:39Z","timestamp":1793039319606,"version":"4.5.0"},"reference-count":204,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T00:00:00Z","timestamp":1709856000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of University and Research"},{"name":"National Recovery and Resilience Plan"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,4,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>An increasing number of individuals are at high risk of type 2 diabetes (T2D) and its cardiovascular complications, including heart failure (HF), chronic kidney disease (CKD), and eventually premature death. The sodium-glucose co-transporter-2 (SGLT2) protein sits in the proximal tubule of human nephrons to regulate glucose reabsorption and its inhibition by gliflozins represents the cornerstone of contemporary T2D and HF management. Herein, we aim to provide an updated overview of the pleiotropy of gliflozins, provide mechanistic insights and delineate related cardiovascular (CV) benefits. By discussing contemporary evidence obtained in preclinical models and landmark randomized controlled trials, we move from bench to bedside across the broad spectrum of cardio- and cerebrovascular diseases. With landmark randomized controlled trials confirming a reduction in major adverse CV events (MACE; composite endpoint of CV death, non-fatal myocardial infarction, and non-fatal stroke), SGLT2 inhibitors strongly mitigate the risk for heart failure hospitalization in diabetics and non-diabetics alike while conferring renoprotection in specific patient populations. Along four major pathophysiological axes (i.e. at systemic, vascular, cardiac, and renal levels), we provide insights into the key mechanisms that may underlie their beneficial effects, including gliflozins\u2019 role in the modulation of inflammation, oxidative stress, cellular energy metabolism, and housekeeping mechanisms. We also discuss how this drug class controls hyperglycaemia, ketogenesis, natriuresis, and hyperuricaemia, collectively contributing to their pleiotropic effects. Finally, evolving data in the setting of cerebrovascular diseases and arrhythmias are presented and potential implications for future research and clinical practice are comprehensively reviewed.<\/jats:p>","DOI":"10.1093\/cvr\/cvae047","type":"journal-article","created":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T10:18:12Z","timestamp":1709806692000},"page":"443-460","source":"Crossref","is-referenced-by-count":193,"title":["SGLT2 inhibitors: from glucose-lowering to cardiovascular benefits"],"prefix":"10.1093","volume":"120","author":[{"given":"Alberto","family":"Preda","sequence":"first","affiliation":[{"name":"Department of Clinical Cardiology, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0823-8729","authenticated-orcid":false,"given":"Fabrizio","family":"Montecucco","sequence":"additional","affiliation":[{"name":"First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa , 6 viale Benedetto XV, 16132 Genoa ,","place":["Italy"]},{"name":"IRCCS Ospedale Policlinico San Martino Genoa\u2014Italian Cardiovascular Network , Genoa ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6909-0150","authenticated-orcid":false,"given":"Federico","family":"Carbone","sequence":"additional","affiliation":[{"name":"First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa , 6 viale Benedetto XV, 16132 Genoa ,","place":["Italy"]},{"name":"IRCCS Ospedale Policlinico San Martino Genoa\u2014Italian Cardiovascular Network , Genoa ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni G","family":"Camici","sequence":"additional","affiliation":[{"name":"Center for Molecular Cardiology, University of Z\u00fcrich , Schlieren ,","place":["Switzerland"]},{"name":"Department of Research and Education, University Hospital Zurich , Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas F","family":"L\u00fcscher","sequence":"additional","affiliation":[{"name":"Center for Molecular Cardiology, University of Z\u00fcrich , Schlieren ,","place":["Switzerland"]},{"name":"Royal Brompton and Harefield Hospitals and Imperial College and King\u2019s College , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8245-7287","authenticated-orcid":false,"given":"Simon","family":"Kraler","sequence":"additional","affiliation":[{"name":"Center for Molecular Cardiology, University of Z\u00fcrich , Schlieren ,","place":["Switzerland"]},{"name":"Department of Internal Medicine, Cantonal Hospital Baden , Baden ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1472-7975","authenticated-orcid":false,"given":"Luca","family":"Liberale","sequence":"additional","affiliation":[{"name":"First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa , 6 viale Benedetto XV, 16132 Genoa ,","place":["Italy"]},{"name":"IRCCS Ospedale Policlinico San Martino Genoa\u2014Italian Cardiovascular Network , Genoa ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,3,8]]},"reference":[{"key":"2025041611021254900_cvae047-B1","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.diabres.2013.11.002","article-title":"Global estimates of diabetes prevalence for 2013 and projections for 2035","volume":"103","author":"Guariguata","year":"2014","journal-title":"Diabetes Res Clin 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