New-onset syncope in diabetic patients treated with sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase 4 inhibitors: A Chinese population-based cohort study

Abstract Background and Aims Type 2 diabetes mellitus (T2DM) is an independent risk factor for syncope. Sodium-glucose cotransporter-2 inhibitor (SGLT2i) shows strong cardiovascular benefits, but a therapeutic benefit on syncope has not been previously investigated. This study aims to investigate the incidence of new-onset syncope in T2DM patients treated with SGLT2i v.s. dipeptidyl peptidase-4 inhibitors (DPP4i) in a Chinese population. Methods This was a retrospective cohort study of T2DM patients treated with SGLT2i or DPP4i between January 1st, 2016, and December 31st, 2020, in Hong Kong. The study outcomes were new-onset syncope, cardiovascular mortality and all-cause mortality. Results A total of 55370 patients (50.48% male; median age: 62.78 years) were included with a median follow-up of 5.56 years. In the matched cohort (SGLT2i: n=18751; DPP4i: n=18751), SGLT2i use was significantly associated with lower risks of syncope (HR: 0.49, 95%CI: [0.41, 0.57], P < 0.0001), cardiovascular mortality (HR: 0.35, 95%CI: [0.26, 0.46], P < 0.001) and all-cause mortality (HR: 0.30, 95%CI: [0.26, 0.34], P < 0.0001). Of the SGLT2i types, empagliflozin (HR: 0.79, 95%CI: [0.59, 1.05], P = 0.0999), dapagliflozin (HR: 0.70, 95%CI: [0.58, 0.85], P = 0.0004), canagliflozin (HR: 0.48, 95%CI: [0.36, 0.63], P < 0.0001) and ertugliflozin (HR: 0.45, 95%CI: [0.30, 0.68], P = 0.0001) were all associated with significantly lower risks of syncope. Conclusions SGLT2i is associated with lower risk of new-onset syncope, cardiovascular death and all-cause death compared to DPP4i. Of the different SGLT2i, dapagliflozin, canagliflozin and ertuglifolzin were significantly associated with lower risks of new-onset syncope.