Efficacy and tolerability of vildagliptin vs. pioglitazone when added to metformin: a 24-week, randomized, double-blind study

Aim: The aim of this study was to compare the efficacy and tolerability of vildagliptin vs. pioglitazone as add-on therapy in patients with type 2 diabetes inadequately controlled with metformin monotherapy. Methods: This 24-week, multicentre, double-blind, randomized, active-controlled study compared vildagliptin (100 mg daily, given as equally divided doses, n = 295) and pioglitazone (30 mg daily, given as a single q.d. dose, n = 281) in patients with inadequate glycaemic control (A1C 7.5-11%) while receiving a stable metformin dose (>= 1500 mg daily). The adjusted mean changes from baseline to study endpoint (AM Delta) in A1C, fasting plasma glucose (FPG), fasting lipids and body weight were compared by analysis of covariance. Results: When added to a stable dose of metformin (mean dose at baseline > 2000 mg/day), both vildagliptin and pioglitazone decreased A1C (AM Delta = -0.9 +/- 0.1% and -1.0 +/- 0.1%, respectively) from identical baseline values (8.4 +/- 0.1%). The between-group difference in AM Delta A1C was 0.1 +/- 0.1%, and non-inferiority of vildagliptin to pioglitazone was established at both 0.4 and 0.3% margins for upper limit of the 95% confidence intervals. Pioglitazone decreased FPG (AM Delta = -2.1 +/- 0.1 mmol/l) to a greater extent than vildagliptin (AM Delta = -1.4 +/- 0.1 mmol/l), but only pioglitazone increased body weight (AM Delta = +1.9 +/- 0.2 kg: between-group difference = -1.6 +/- 0.3 kg, p < 0.001). Adverse events (AEs) were reported by 60% of vildagliptin-treated patients and by 56.4% of pioglitazone-treated patients; serious AEs were reported by 2.0 and 4.6% of patients receiving vildagliptin and pioglitazone respectively. Mild hypoglycaemia was reported by one patient (0.3%) in the vildagliptin group and by no patients receiving pioglitazone. Conclusions: When added to metformin, the efficacy of vildagliptin is non-inferior to that of pioglitazone. The treatments were similarly well tolerated, but only pioglitazone increased body weight.