Increase in overall mortality risk in patients with type 2 diabetes receiving glipizide, glyburide or glimepiride monotherapy versus metformin: a retrospective analysis

Diabetes Obes Metab. 2012 Sep;14(9):803-9. doi: 10.1111/j.1463-1326.2012.01604.x. Epub 2012 Apr 29.


Aims: It remains uncertain if differences in mortality risk exist among the sulfonylureas, especially in patients with documented coronary artery disease (CAD). The purpose of this study was to assess the overall mortality risk of the individual sulfonylureas versus metformin in a large cohort of patients with type 2 diabetes.

Methods: A retrospective cohort study was conducted using an academic health centre enterprise-wide electronic health record (EHR) system to identify 23 915 patients with type 2 diabetes who initiated monotherapy with metformin (N = 12774), glipizide (N = 4325), glyburide (N = 4279) or glimepiride (N = 2537), ≥ 18 years of age, with and without a history of CAD, and not on insulin or a non-insulin injectable at baseline. The patients were followed for mortality by documentation in the EHR and Social Security Death Index. Multivariable Cox models with propensity analysis were used to compare cohorts.

Results: An increase in overall mortality risk was observed in the entire cohort with glipizide (HR 1.64; 95% CI 1.39-1.94), glyburide (HR 1.59; 95% CI 1.35-1.88), and glimepiride (HR 1.68; 95% CI 1.37-2.06) versus metformin; however, in those patients with documented CAD, a statistically significant increase in overall mortality risk was only found with glipizide (HR 1.41; 95% CI 1.07-1.87) and glyburide (HR 1.38; 95% CI 1.04-1.83) versus metformin.

Conclusions: Glipizide, glyburide and glimepiride are associated with an increased risk of overall mortality versus metformin. Our results suggest that if a sulfonylurea is required to obtain glycaemic control, glimepiride may be the preferred sulfonylurea in those with underlying CAD.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / mortality
  • Female
  • Glipizide / therapeutic use
  • Glyburide / therapeutic use
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Kaplan-Meier Estimate
  • Male
  • Metformin / therapeutic use
  • Middle Aged
  • Propensity Score
  • Retrospective Studies
  • Sulfonylurea Compounds / therapeutic use
  • Young Adult


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