Sodium-glucose cotransporter-2 inhibitor use in type 2 diabetes mellitus is associated with a lower rate of atrial arrhythmias in a hospitalized real-world population

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have been associated with lower rates of cardiac arrhythmias in post hoc analyses. The real-world effect on cardiac arrhythmias is incompletely defined. 

Objective: The purpose of this study was to determine the effects of SGLT2i on cardiac arrhythmias in a real-world, hospitalized population. 

Methods: A retrospective cohort study was performed in South Australia, Australia. Patients (n = 882) with type 2 diabetes mellitus (T2DM) on oral diabetic therapy (33.6% females, median age 62.3 years) who received SGLT2i (for T2DM) were identified through public hospital admissions from 2011–2019. Patients were matched with 3282 contemporaneous controls with T2DM who did not receive SGLT2i. Baseline characteristics were adjusted using inverse probability treatment weighting. The primary outcome was incidence of atrial arrhythmias. Secondary outcomes included incidence of ventricular arrhythmias and cardiac arrest at 2 years. 

Results: All-cause mortality was higher in the SGLT2i group (hazard ratio [HR] 2.02, 95% confidence interval [CI] 1.55–2.63, P <.001) despite propensity matching, highlighting the greater unmeasured comorbidity burden of the SGLT2i-treated group. Despite this, SGLT2i treatment was associated with fewer atrial arrhythmias (HR 0.17, 95% CI 0.07–0.41, P <.001) at 2 years. The relationship between SGLT2i use and ventricular arrhythmias (HR 0.25, 95% CI 0.06–1.03, P = .055) and cardiac arrest (HR 0.82, 95% CI 0.20–3.45, P = .796) did not reach statistical significance. 

Conclusion: In this real-world, comorbid inpatient cohort, SGLT2i treatment was associated with a lower incidence of atrial arrhythmias. Prospective randomized trials evaluating SGLT2i as specific atrial fibrillation pharmacotherapy are underway.