Secondary failure rates associated with metformin and sulfonylurea therapy for type 2 diabetes mellitus

Study Objective. To determine whether metformin therapy, compared with sulfonylurea therapy, is associated with a delayed onset of secondary failure in patients with type 2 diabetes mellitus. Design. Retrospective cohort study Data Source. Outpatient prescription database from Saskatchewan Health, Saskatchewan, Canada. Patients. Two cohorts-5077 individuals receiving sulfonylurea monotherapy and 1652 receiving metformin monotherapy for 2 years or longer-identified from a population of 12,272 new users of oral antidiabetic agents between 1991 and 1996 and who were followed through 1999. Measurements and Main Results. The association between initial drug therapy and onset of secondary failure was evaluated using multivariate Cox proportional hazard models in which the sulfonylurea monotherapy cohort was the reference group. Secondary failure was defined as progression to combination oral therapy or a switch in oral therapy; each component (e.g., time to combination therapy or first switch) of this definition, including start of insulin therapy, was assessed as a secondary outcome. The subjects' mean age was 63.8 years, and 3787 (56.3%) were men. Subjects were followed for a mean +/- SD of 5.7 +/- 1.8 years. Metformin monotherapy was associated with a delay in the onset of secondary failure (hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.82-0.98), in the progression to combination therapy (HR 0.79, 95% CI 0.71-0.87), and in the start of insulin therapy (HR 0.65, 95% CI 0.51-0.82). Of note, patients receiving metformin monotherapy first were more likely than those receiving sulfonylurea monotherapy first to switch treatments (HR 1.43, 95% CI 1.17-1.75). Conclusion. Compared with sulfonylurea therapy, metformin therapy appears to be associated with a delay in the onset of secondary failure.