Comparative Effectiveness of Sodium-Glucose Cotransporter 2 Inhibitors vs the Other Hypoglycemic Drugs on Major Adverse Cardiovascular Events and Hospitalization for Heart Failure in Patients with Type 2 Diabetes Mellitus and Atrial Fibrillation

Abstract

Background: In the treatment of type 2 diabetes mellitus (T2DM) in atrial fibrillation (AF) patients, evidence of the comparative effectiveness of sodium-glucose cotransporter 2 (SGLT2) inhibitors vs the other hypoglycemic drugs on cardiovascular morbidity and mortality is lacking. This study aimed to evaluate the comparative effectiveness of SGLT2 inhibitors vs the other hypoglycemic drugs on major adverse cardiovascular events and heart failure for hospitalization in patients with T2DM and AF.Methods: A cohort study used data from the Korean National Health Insurance Service database compared the use of SGLT2 inhibitors vs the other hypoglycemic drugs for treatment of T2DM in AF patients. We identified 40,268 patients with T2DM and AF who were newly prescribed oral hypoglycemic drugs (2,977 individualst with SGLT2 inhibitors and 37,291 individuals without SGLT2 inhibitors) between 2014 and 2018. After 1:4 propensity score matching, patients who received SGLT2 inhibitors (n=2,958) and those who did not receive SGLT2 inhibitors (n=10,691) were enrolled, and followed up until December 31, 2018. The primary study outcome was major adverse cardiovascular events (MACE), a composite of cardiovascular mortality, myocardial infarction, or ischemic stroke. Secondary outcoms were hospitalization for heart failure and all-cause mortality. The risks of study outcomes were assessed using a Cox proportional hazard model.Results: Mean age of all participants was 59.7 ± 11.9 years and 8.023 [58%] were male. During a mean follow-up duration of 2.1 ± 1.4 years, SGLT2 inhibitors were not significantly associated with reduced risk of MACE(hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.76-1.21) compared with the other hypoglycemic drugs. However, patients who received SGLT2 inhibitors had significantly lower risks of hospitalization for heart failure (HR, 0.70; 95% CI, 0.53-0.93) and all-cause mortality (HR, 0.74; 95% CI, 0.56-0.98) than those who did not receive SGLT2 inhibitors. Conclusions: In this real-world cohort of Asian patients with T2DM and AF, new use of SGLT2 inhibitors was associated with a lower risk of hospitalization for heart failure compared with use of the other hypoglycemic drugs.