{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:04:08Z","timestamp":1792789448442,"version":"4.5.0"},"reference-count":22,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T00:00:00Z","timestamp":1681171200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute for Health Research Applied Research Collaboration North West Coast (ARC NWC)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are effective anti-diabetic drugs improving cardiovascular outcomes in type 2 diabetes mellitus (T2DM) patients. This study investigated cardiovascular, cerebrovascular and cognitive outcomes of SGLT2i therapy in patients with atrial fibrillation (AF) and T2DM. Methods: Observational study using TriNetX, a global health research network of anonymised electronic medical records from real-world patients between January 2018 and December 2019. The network includes healthcare organisations globally but predominately in the United States. AF patients (ICD-10-CM code: I48) with T2DM were divided according to SGLT2i use or not, and balanced using propensity score matching (PSM). Patients were followed-up for 3-years. The primary endpoints were ischaemic stroke\/transient ischemic attack (TIA), intracranial haemorrhage (ICH), and incident dementia. Secondary endpoints were incident heart failure and mortality. Results: We identified 89,356 AF patients with T2DM of which 5061 (5.7%) were taking a SGLT2i. After PSM, 5049 patients (mean age 66.7 \u00b1 10.6 years; 28.9% female) were included in each group. At 3-years follow-up, the risk of ischaemic stroke\/TIA was higher in patients not receiving SGLT2i (HR 1.12, 95% CI 1.01\u20131.24) and for ICH (HR 1.57, 95% CI 1.25\u20131.99) and incident dementia (HR 1.66, 95% CI 1.30\u20132.12). Incident heart failure (HR 1.50, 95% CI 1.34\u20131.68) and mortality (HR 1.77, 95% CI 1.58\u20131.99) risks were increased in AF patients not receiving SGLT2i. Conclusions: In our large \u2018real world\u2019 analysis of patients with concomitant AF and T2DM, SGLT2i reduced the risk of cerebrovascular events, incident dementia, heart failure and death.<\/jats:p>","DOI":"10.3390\/jcm12082814","type":"journal-article","created":{"date-parts":[[2023,4,12]],"date-time":"2023-04-12T02:08:11Z","timestamp":1681265291000},"page":"2814","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Cerebrovascular, Cognitive and Cardiac Benefits of SGLT2 Inhibitors Therapy in Patients with Atrial Fibrillation and Type 2 Diabetes Mellitus: Results from a Global Federated Health Network Analysis"],"prefix":"10.3390","volume":"12","author":[{"given":"Riccardo","family":"Proietti","sequence":"first","affiliation":[{"name":"Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool L8 7TX, UK"},{"name":"Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L8 7TX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0492-6241","authenticated-orcid":false,"given":"Jos\u00e9 Miguel","family":"Rivera-Caravaca","sequence":"additional","affiliation":[{"name":"Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool L8 7TX, UK"},{"name":"Department of Cardiology, Hospital Cl\u00ednico Universitario Virgen de la Arrixaca, University of Murcia, Instituto Murciano de Investigaci\u00f3n Biosanitaria (IMIB-Arrixaca), CIBERCV, 30120 Murcia, Spain"},{"name":"School of Nursing, University of Murcia, 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"L\u00f3pez-G\u00e1lvez","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hospital Cl\u00ednico Universitario Virgen de la Arrixaca, University of Murcia, Instituto Murciano de Investigaci\u00f3n Biosanitaria (IMIB-Arrixaca), CIBERCV, 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie L.","family":"Harrison","sequence":"additional","affiliation":[{"name":"Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool L8 7TX, UK"},{"name":"Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L8 7TX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7246-7708","authenticated-orcid":false,"given":"Francisco","family":"Mar\u00edn","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hospital Cl\u00ednico Universitario Virgen de la Arrixaca, University of Murcia, Instituto Murciano de Investigaci\u00f3n Biosanitaria (IMIB-Arrixaca), CIBERCV, 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Underhill","sequence":"additional","affiliation":[{"name":"TriNetX LLC, London EC3V 4AB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduard","family":"Shantsila","sequence":"additional","affiliation":[{"name":"Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool L8 7TX, UK"},{"name":"Department of Primary Care and Mental Health, University of Liverpool, Liverpool L8 7TX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2880-5236","authenticated-orcid":false,"given":"Garry","family":"McDowell","sequence":"additional","affiliation":[{"name":"Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool L8 7TX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1768-3894","authenticated-orcid":false,"given":"Manlio","family":"Vinciguerra","sequence":"additional","affiliation":[{"name":"Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool L8 7TX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhys","family":"Davies","sequence":"additional","affiliation":[{"name":"The Walton Centre NHS Foundation Trust, Lower Lane, Liverpool L9 7LJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0746-0566","authenticated-orcid":false,"given":"Clarissa","family":"Giebel","sequence":"additional","affiliation":[{"name":"Department of Primary Care and Mental Health, University of Liverpool, Liverpool L8 7TX, UK"},{"name":"NIHR Applied Research Collaboration North West Coast, Liverpool L8 7TX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deirdre A.","family":"Lane","sequence":"additional","affiliation":[{"name":"Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool L8 7TX, UK"},{"name":"Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L8 7TX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7566-1626","authenticated-orcid":false,"given":"Gregory Y. H.","family":"Lip","sequence":"additional","affiliation":[{"name":"Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool L8 7TX, UK"},{"name":"Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L8 7TX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/S0140-6736(21)00536-5","article-title":"SGLT2 inhibitors and GLP-1 receptor agonists: Established and emerging indications","volume":"398","author":"Brown","year":"2021","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1007\/s10741-020-10038-w","article-title":"SGLT2-inhibitors; more than just glycosuria and diuresis","volume":"26","author":"Fathi","year":"2021","journal-title":"Heart Fail. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1056\/NEJMoa1504720","article-title":"Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes","volume":"373","author":"Zinman","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1056\/NEJMoa1611925","article-title":"Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes","volume":"377","author":"Neal","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1056\/NEJMoa1812389","article-title":"Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes","volume":"380","author":"Wiviott","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1056\/NEJMoa1811744","article-title":"Canagliflozin and renal outcomes in type 2 diabetes and nephropathy","volume":"380","author":"Perkovic","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1161\/STROKEAHA.120.031623","article-title":"Effect of SGLT2 inhibitors on stroke and atrial fibrillation in diabetic kidney disease: Results from the CREDENCE trial and meta-analysis","volume":"52","author":"Zhou","year":"2021","journal-title":"Stroke"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1161\/CIRCULATIONAHA.119.044183","article-title":"Effect of dapagliflozin on atrial fibrillation in patients with type 2 diabetes mellitus: Insights from the DECLARE-TIMI 58 Trial","volume":"141","author":"Zelniker","year":"2020","journal-title":"Circulation"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1001\/jama.2015.13480","article-title":"The propensity score","volume":"314","author":"Haukoos","year":"2015","journal-title":"JAMA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.ccl.2015.12.011","article-title":"Atrial Fibrillation and Cognitive Decline","volume":"34","author":"Kalantarian","year":"2016","journal-title":"Cardiol. Clin."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1016\/j.hrthm.2012.07.026","article-title":"Atrial fibrillation and the risk of incident dementia: A meta-analysis","volume":"9","author":"Santangeli","year":"2012","journal-title":"Heart Rhythm."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"106","DOI":"10.2459\/JCM.0000000000000917","article-title":"The association between atrial fibrillation and Alzheimer\u2019s disease: Fact or fallacy? A systematic review and meta-analysis","volume":"21","author":"Proietti","year":"2020","journal-title":"J. Cardiovasc. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1161\/STROKEAHA.117.019189","article-title":"Prospective study of fasting blood glucose and intracerebral hemorrhagic risk","volume":"49","author":"Jin","year":"2018","journal-title":"Stroke"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/bs.irn.2020.03.018","article-title":"A role for sodium glucose cotransporter 2 inhibitors (SGLT2is) in the treatment of Alzheimer\u2019s disease?","volume":"155","author":"Esterline","year":"2020","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.1007\/s00125-018-4675-2","article-title":"Effects of dapagliflozin and n-3 carboxylic acids on non-alcoholic fatty liver disease in people with type 2 diabetes: A double-blind randomised placebo-controlled study","volume":"61","author":"Eriksson","year":"2018","journal-title":"Diabetologia"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1161\/STROKEAHA.118.023009","article-title":"Canagliflozin and Stroke in Type 2 Diabetes Mellitus: Results from the Randomized CANVAS Program Trials","volume":"50","author":"Zhou","year":"2019","journal-title":"Stroke"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/s12933-021-01293-8","article-title":"Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and cardiac arrhythmias: A systematic review and meta-analysis","volume":"20","author":"Li","year":"2021","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1007\/s00125-018-4670-7","article-title":"SGLT2 inhibitors and mechanisms of cardiovascular benefit: A state-of-the-art review","volume":"61","author":"Verma","year":"2018","journal-title":"Diabetologia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"R113","DOI":"10.1530\/EJE-17-0832","article-title":"SGLT2 inhibitors: Clinical benefits by restoration of normal diurnal metabolism?","volume":"178","author":"Esterline","year":"2018","journal-title":"Eur. J. Endocrinol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.1056\/NEJMoa1911303","article-title":"Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction","volume":"381","author":"McMurray","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1056\/NEJMoa2022190","article-title":"Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure","volume":"383","author":"Packer","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1056\/NEJMoa2107038","article-title":"Empagliflozin in Heart Failure with a Preserved Ejection Fraction","volume":"385","author":"Anker","year":"2021","journal-title":"N. Engl. J. Med."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/8\/2814\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:14:04Z","timestamp":1760123644000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/8\/2814"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,11]]},"references-count":22,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["jcm12082814"],"URL":"https:\/\/doi.org\/10.3390\/jcm12082814","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,11]]}}}