Sulfonylurea is associated with higher risks of ventricular arrhythmia or sudden cardiac death compared to metformin: a population-based cohort study

Abstract

Background: Commonly prescribed diabetic medications such as metformin and sulfonylurea may be associated with different arrhythmogenic risks. This study compared the risk of ventricular arrhythmia or sudden cardiac death (VA/SCD) between metformin and sulfonylurea in patients with type 2 diabetes. Methods: Patients aged 40 years or older who were diagnosed with type-2 diabetes mellitus or prescribed anti-diabetic agents in Hong Kong between 1st January 2009 and 31st December 2009 were included and followed up till 31st December 2019. Patients prescribed with both metformin and sulfonylurea or had prior myocardial infarction were excluded. The study outcome was a composite of VA/SCD. Metformin users and sulfonylurea users were matched at a 1:1 ratio by propensity score matching. Results: The study cohort consisted of 5756 metformin users (48.00% male, age 68±11 years, mean follow-up 5.04±2.57 years) and 5756 sulfonylurea users (50.30% male, age 69±11 years, mean follow-up 5.04±2.54 years). Sulfonylurea was associated with higher risk of VA/SCD than metformin (hazard ratio 1.84 [1.56 - 2.16], p<0.001). Such difference was consistently observed in subgroup analyses stratifying for insulin usage or known coronary heart disease. Conclusion: Sulfonylurea use is associated with higher risk of VA/SCD than metformin in patients with type 2 diabetes.