Higher Risk of Hypoglycemia with Glimepiride Versus Vildagliptin in Patients with Type 2 Diabetes is not Driven by High Doses of Glimepiride: Divergent Patient Susceptibilities?

Abstract

Introduction: In a previously published study, vildagliptin showed a reduced risk of hypoglycemia versus glimepiride as add-on therapy to metformin at similar efficacy. Glimepiride was titrated from a starting dose of 2 mg/day to a maximum dose of 6 mg/day. It is usually assumed that the increased hypoglycemia with glimepiride was driven by the 6 mg/day dose; it was therefore of interest to assess whether the risk of hypoglycemia is also different between vildagliptin and a low (2 mg/day) dose of glimepiride., Methods: Data (n = 3,059) were from the aforementioned randomized, double-blind study. Comparisons between vildagliptin (50 mg twice daily) and glimepiride (subgroups of patients on 2 mg/day, 6 mg/day, and 'other', and overall glimepiride group) were done by modeling hypoglycemia risk as a function of time and last-measured glycated hemoglobin (HbA1c) using discrete event time modeling, with treatment, age, gender as additional covariates., Results: The hypoglycemia risk was significantly lower in patients receiving vildagliptin versus patients remaining on glimepiride 2 mg/day throughout the study, with similar results unadjusted or adjusted for last HbA1c [adjusted hazard ratio (HR) = 0.06 (95% CI 0.03, 0.11)]. The risk of hypoglycemia was very low with vildagliptin over the full HbA1c range, while the risk with glimepiride 2 mg/day increased with lower HbA1c. The increase for lower levels of HbA1c was more pronounced in the glimepiride 2 mg/day than 6 mg/day subgroup, with the 6 mg/day subgroup showing the lowest hypoglycemia risk among the glimepiride groups [adjusted HR vildagliptin vs. 6 mg/day glimepiride = 0.21 (95% CI 0.11, 0.40)]., Conclusion: The data show a substantially lower risk of confirmed hypoglycemia with vildagliptin compared to low-dose (2 mg/day) glimepiride. The analysis indicates that the previously reported results are not driven by high doses of glimepiride and points to interesting differences among patients regarding the susceptibility to hypoglycemia with sulfonylureas.