Sulfonylurea Is Associated With Higher Risks of Ventricular Arrhythmia or Sudden Cardiac Death Compared With Metformin: A Population-Based Cohort Study

J Am Heart Assoc. 2022 Sep 20;11(18):e026289. doi: 10.1161/JAHA.122.026289. Epub 2022 Sep 14.

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 between metformin and sulfonylurea users in patients with type 2 diabetes. Methods and Results Patients aged ≥40 years who were diagnosed with type 2 diabetes or prescribed antidiabetic agents in Hong Kong between January 1, 2009, and December 31, 2009, were included and followed up until December 31, 2019. Patients prescribed with both metformin and sulfonylurea or had prior myocardial infarction were excluded. The study outcome was a composite of ventricular arrhythmia or sudden cardiac death. Metformin users and sulfonylurea users were matched at a 1:1 ratio by propensity score matching. The matched cohort consisted of 16 596 metformin users (47.70% men; age, 68±11 years; mean follow-up, 4.92±2.55 years) and 16 596 sulfonylurea users (49.80% men; age, 70±11 years; mean follow-up, 4.93±2.55 years). Sulfonylurea was associated with higher risk of ventricular arrhythmia or sudden cardiac death than metformin hazard ratio (HR, 1.90 [95% CI, 1.73-2.08]). Such difference was consistently observed in subgroup analyses stratifying for insulin usage or known coronary heart disease. Conclusions Sulfonylurea use is associated with higher risk of ventricular arrhythmia or sudden cardiac death than metformin in patients with type 2 diabetes.

Keywords: metformin; sudden cardiac death; sulfonylurea; type 2 diabetes; ventricular arrhythmia.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Arrhythmias, Cardiac / chemically induced
  • Arrhythmias, Cardiac / complications
  • Arrhythmias, Cardiac / epidemiology
  • Cohort Studies
  • Death, Sudden, Cardiac / epidemiology
  • Death, Sudden, Cardiac / etiology
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / epidemiology
  • Female
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Insulin / therapeutic use
  • Male
  • Metformin* / adverse effects
  • Middle Aged
  • Retrospective Studies
  • Sulfonylurea Compounds / adverse effects

Substances

  • Hypoglycemic Agents
  • Insulin
  • Sulfonylurea Compounds
  • Metformin