{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,13]],"date-time":"2026-11-13T08:47:26Z","timestamp":1794559646681,"version":"4.9.1"},"reference-count":59,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T00:00:00Z","timestamp":1699920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170327"],"award-info":[{"award-number":["82170327"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370332"],"award-info":[{"award-number":["82370332"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Tianjin Key Medical Discipline (Specialty) Construction Project","award":["TJYXZDXK-029A"],"award-info":[{"award-number":["TJYXZDXK-029A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,2,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and aims<\/jats:title>\n                    <jats:p>Syncope is a symptom that poses an important diagnostic and therapeutic challenge, and generates significant cost for the healthcare system. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated beneficial cardiovascular effects, but their possible effects on incident syncope have not been fully investigated. This study compared the effects of SGLT2i and dipeptidyl peptidase-4 inhibitors (DPP4i) on new-onset syncope.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>This was a retrospective, territory-wide cohort study enrolling type 2 diabetes mellitus (T2DM) patients treated with SGLT2i or DPP4i between 1 January 2015 and 31 December 2020, in Hong Kong, China. The outcomes were hospitalization of new-onset syncope, cardiovascular mortality, and all-cause mortality. Multivariable Cox regression and different approaches using the propensity score were applied to evaluate the association between SGLT2i and DPP4i with incident syncope and mortality. After matching, a total of 37\u2009502 patients with T2DM were included (18\u2009751 SGLT2i users vs. 18\u2009751 DPP4i users). During a median follow-up of 5.56 years, 907 patients were hospitalized for new-onset syncope (2.41%), and 2346 patients died from any cause (6.26%), among which 471 deaths (1.26%) were associated with cardiovascular causes. Compared with DPP4i users, SGLT2i therapy was associated with a 51% lower risk of new-onset syncope [HR 0.49; 95% confidence interval (CI) 0.41\u20130.57; P\u00a0&amp;lt;\u00a00.001], 65% lower risk of cardiovascular mortality (HR 0.35; 95% CI 0.26\u20130.46; P\u00a0&amp;lt;\u00a00.001), and a 70% lower risk of all-cause mortality (HR 0.30; 95% CI 0.26\u20130.34; P\u00a0&amp;lt;\u00a00.001) in the fully adjusted model. Similar associations with syncope were observed for dapagliflozin (HR 0.70; 95% CI 0.58\u20130.85; P\u00a0&amp;lt;\u00a00.001), canagliflozin (HR 0.48; 95% CI 0.36\u20130.63; P\u00a0&amp;lt;\u00a00.001), and ertugliflozin (HR 0.45; 95% CI 0.30\u20130.68; P\u00a0&amp;lt;\u00a00.001), but were attenuated for empagliflozin (HR 0.79; 95% CI 0.59\u20131.05; P\u00a0=\u00a00.100) after adjusting for potential confounders. The subgroup analyses suggested that, compared with DPP4i, SGLT2i was associated with a significantly decreased risk of incident syncope among T2DM patients, regardless of gender, age, glucose control status, Charlson comorbidity index, and the association remained constant amongst those with common cardiovascular drugs and most antidiabetic drugs at baseline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Compared with DPP4i, SGLT2i was associated with a significantly lower risk of new-onset syncope in patients with T2DM, regardless of gender, age, degree of glycaemic control, and comorbidity burden.<\/jats:p>\n                  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Moores University and Liverpool Heart & Chest Hospital , Liverpool , UK"},{"name":"Department of Clinical Medicine, Aalborg University , Aalborg , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingpeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacy, LKS Faculty of Medicine, and the Musketeers Foundation Institute of Data Science, University of Hong Kong , Hong Kong , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Tse","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University , Tianjin 300211 , China"},{"name":"School of Nursing and Health Studies, Hong Kong Metropolitan University , Hong Kong , 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