The association between SGLT2 inhibitors and new-onset arrhythmias: a nationwide population-based longitudinal cohort study

Abstract

Abstract Background/Introduction Clinical trials have shown the cardiovascular protective effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors and reduced hospitalization for heart failure. However, no study has investigated the association between SGLT2 inhibitors and the risk of arrhythmias. Purpose To evaluate the risk of new-onset arrhythmias (NOA) and all-cause mortality with the use of SGLT2 inhibitors. Methods This was a population-based cohort study utilizing Taiwan's National Health Insurance Research Database. Each patient aged 20 years and older who took SGLT2 inhibitors was assigned to the SGLT2 inhibitor group, whereas sex-, age-, diabetes mellitus duration-, drug index date-, and propensity score-matched randomly selected patients without SGLT2 inhibitors were assigned to the non-SGLT2 inhibitor group. The study outcome was all-cause mortality and NOA. Results A total of 399,810 patients newly diagnosed with type 2 diabetes mellitus (T2DM) were enrolled. A 1:1 matching propensity method was used to match 79,150 patients to 79,150 controls in the non-SGLT2 inhibitors group for analysis. The SGLT2 inhibitor group was associated with a lower risk of all-cause mortality (adjusted hazard ratio [aHR] 0.547; 95% confidence interval [CI] 0.482–0.621; P=0.0001) and NOA (aHR 0.830; 95% CI 0.751–0.916; P=0.0002). Subgroup analysis revealed that the SGLT2 inhibitor group was associated with a lower risk of all-cause mortality in all age and severity of the adapted Diabetes Complication Severity Index (aDCSI) subgroups. Furthermore, NOA and atrial fibrillation were associated with a lower risk in subgroups with an aDCSI score of between 1 and 2. Conclusions Patients with T2DM prescribed with SGLT2 inhibitors were associated with a lower risk of all-cause mortality and NOA compared with those not taking SGLT2 inhibitors in real-world practice. The potential protective effect of NOA and atrial fibrillation is observed, especially in individuals with T2DM and an aDCSI score of between 1 and 2. Funding Acknowledgement Type of funding source: Private hospital(s). Main funding source(s): This study was supported in parts by grants from Chung Shan Medical University Hospital.