The Risk of Overall Mortality in Patients With Type 2 Diabetes Receiving Different Combinations of Sulfonylureas and Metformin: A Retrospective Analysis

Diabet Med. 2012 Aug;29(8):1029-35. doi: 10.1111/j.1464-5491.2012.03577.x.


Aims: Sulfonylureas have been shown to increase mortality when used in combination with metformin. This may not be a class effect of sulfonylureas, but rather secondary to differences in properties inherent to the individual sulfonylureas (hypoglycaemic risk, sulfonylurea receptor selectivity and effects on myocardial ischemic preconditioning). The purpose of this study was to assess the risk of overall mortality in patients with Type 2 diabetes treated with different combinations of sulfonylureas and metformin.

Methods: A retrospective cohort study was conducted using an academic health center enterprise-wide electronic health record system to identify 7320 patients with Type 2 diabetes (3768 initiators of glyburide (glibenclamide) and metformin, 2277 initiators of glipizide and metformin and 1275 initiators of glimepiride and metformin), ≥ 18 years of age and not on insulin or a non-insulin injectable at baseline. The patients were followed for mortality by documentation in the electronic health record and Social Security Death Index. Multivariable Cox models with propensity analysis were used to compare cohorts.

Results: No statistically significant difference in overall mortality risk was observed among the different combinations of sulfonylureas and metformin: glimepiride and metformin vs. glipizide and metformin (HR 1.03; 95% CI 0.89-1.20), glimepiride and metformin vs. glyburide (glibenclamide) and metformin (HR 1.08; 95% CI 0.90-1.30), or with glipizide and metformin vs. glyburide (glibenclamide) and metformin (HR 1.05; 95% CI 0.95-1.15).

Conclusions: Our results did not identify an increased mortality risk among the different combinations of sulfonylureas and metformin, suggesting that overall mortality is not substantially influenced by the choice of sulfonylurea.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / mortality
  • Drug Therapy, Combination / methods
  • Female
  • Glipizide / therapeutic use
  • Glyburide / therapeutic use
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Male
  • Metformin / therapeutic use*
  • Middle Aged
  • Retrospective Studies
  • Risk Factors
  • Sulfonylurea Compounds / therapeutic use*


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