The Risk of Overall Mortality in Patients With Type 2 Diabetes Receiving Glipizide, Glyburide, or Glimepiride Monotherapy

OBJECTIVE Sulfonylureas have historically been analyzed as a medication class, which may be inappropriate given the differences in properties inherent to the individual sulfonylureas (hypoglycemic risk, sulfonylurea receptor selectivity, and effects on myocardial ischemic preconditioning). The purpose of this study was to assess the relationship of individual sulfonylureas and the risk of overall mortality in a large cohort of patients with type 2 diabetes. RESEARCH DESIGN AND METHODS A retrospective cohort study was conducted using an academic health center enterprise-wide electronic health record (EHR) system to identify 11,141 patients with type 2 diabetes (4,279 initiators of monotherapy with glyburide, 4,325 initiators of monotherapy with glipizide, and 2,537 initiators of monotherapy with glimepiride), >or=18 years of age with and without a history of coronary artery disease (CAD) and not on insulin or a noninsulin injectable at baseline. The patients were followed for mortality by documentation in the EHR and Social Security Death Index. Multivariable Cox models were used to compare cohorts. RESULTS No statistically significant difference in the risk of overall mortality was observed among these agents in the entire cohort, but we did find evidence of a trend toward an increased overall mortality risk with glyburide versus glimepiride (hazard ratio 1.36 [95% CI 0.96-1.91]) and glipizide versus glimepiride (1.39 [0.99-1.96]) in those with documented CAD. CONCLUSIONS Our results did not identify an increased mortality risk among the individual sulfonylureas but did suggest that glimepiride may be the preferred sulfonylurea in those with underlying CAD.