OBJECTIVES: This study evaluates and compares persistence on therapy with glipizide GITS (Glucotrol XL), glipizide, or glyburide in newly treated type 2 diabetes patients. METHODS: This was a retrospective, longitudinal claims data analysis using enrollment and pharmacy claims data for commercial enrollees in 8 UnitedHealthcare health plans, a national independent practice model managed care health plan. Subjects were 25 years of age or older with a first filled prescription for any of the three study drugs from January 1, 1996 through December 31, 1999. Persistence on therapy was defined as the total days supplied from the first filled prescription until termination of therapy, switch in therapy or augmentation of therapy. Cox proportional hazards analysis was used to compare differences in persistence between study drugs adjusted for covariates. RESULTS: Of the 24,311 new users of oral hypoglycemic agents, 35% filled a first prescription for glipizide GITS, 15% filled glipizide, and 50% filled glyburide. The cox proportional hazards model showed that users of glipizide GITS had significantly better persistence on therapy compared to users of glipizide (p<.001) and users of glyburide (p<.001) in 90 days following the index therapy. Glipizide users were 1.332 times more likely (95% CI:1.251- 1.417) and glyburide users were 1.164 times more likely (95% CI:1.111- 1.220) to discontinue therapy compared to glipizide GITS. CONCLUSIONS: In this study, glipizide GITS appears to have an advantage in terms of persistence on therapy compared to glipizide and glyburide, and important indicator of efficacy. Better persistence may be a result of the extended release formulation of glipizide GITS, requiring only once daily dosing. Cost savings may be realized in overall diabetes-related care for glipizide GITS users if improved persistence to therapy translates into better glucose control over time.