Comparative Safety of Sulfonylureas and the Risk of Sudden Cardiac Arrest and Ventricular Arrhythmia

Diabetes Care. 2018 Apr;41(4):713-722. doi: 10.2337/dc17-0294. Epub 2018 Feb 2.


Objective: To examine the association between individual antidiabetic sulfonylureas and outpatient-originating sudden cardiac arrest and ventricular arrhythmia (SCA/VA).

Research design and methods: We conducted a retrospective cohort study using 1999-2010 U.S. Medicaid claims from five large states. Exposures were determined by incident use of glyburide, glimepiride, or glipizide. Glipizide served as the reference exposure, as its effects are believed to be highly pancreas specific. Outcomes were ascertained by a validated ICD-9-based algorithm indicative of SCA/VA (positive predictive value ∼85%). Potential confounding was addressed by adjustment for multinomial high-dimensional propensity scores included as continuous variables in a Cox proportional hazards model.

Results: Of sulfonylurea users under study (N = 519,272), 60.3% were female and 34.9% non-Hispanic Caucasian, and the median age was 58.0 years. In 176,889 person-years of sulfonylurea exposure, we identified 632 SCA/VA events (50.5% were immediately fatal) for a crude incidence rate of 3.6 per 1,000 person-years. Compared with glipizide, propensity score-adjusted hazard ratios for SCA/VA were 0.82 (95% CI 0.69-0.98) for glyburide and 1.10 (0.89-1.36) for glimepiride. Numerous secondary analyses showed a very similar effect estimate for glyburide; yet, not all CIs excluded the null.

Conclusions: Glyburide may be associated with a lower risk of SCA/VA than glipizide, consistent with a very small clinical trial suggesting that glyburide may reduce ventricular tachycardia and isolated ventricular premature complexes. This potential benefit must be contextualized by considering putative effects of different sulfonylureas on other cardiovascular end points, cerebrovascular end points, all-cause death, and hypoglycemia.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Arrhythmias, Cardiac / chemically induced
  • Arrhythmias, Cardiac / epidemiology*
  • Cause of Death
  • Death, Sudden, Cardiac / epidemiology*
  • Death, Sudden, Cardiac / etiology
  • Diabetic Angiopathies / drug therapy
  • Diabetic Angiopathies / epidemiology
  • Female
  • Glipizide / adverse effects
  • Glipizide / therapeutic use
  • Glyburide / adverse effects
  • Glyburide / therapeutic use
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemia / epidemiology
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use
  • Male
  • Middle Aged
  • Retrospective Studies
  • Risk Factors
  • Sulfonylurea Compounds / adverse effects*
  • Sulfonylurea Compounds / therapeutic use
  • United States / epidemiology
  • Ventricular Dysfunction / chemically induced
  • Ventricular Dysfunction / complications
  • Ventricular Dysfunction / epidemiology*


  • Hypoglycemic Agents
  • Sulfonylurea Compounds
  • glimepiride
  • Glyburide
  • Glipizide