Vildagliptin in combination with pioglitazone improves glycaemic control in patients with type 2 diabetes failing thiazolidinedione monotherapy: a randomized, placebo‐controlled study*

Abstract

Aim: The purpose of this study was to assess the efficacy and tolerability of the dipeptidyl peptidase‐4 inhibitor vildagliptin in combination with the thiazolidinedione (TZD) pioglitazone in patients with type 2 diabetes (T2DM). Methods: This was a 24‐week, multicentre, double‐blind, randomized, parallel‐group study comparing the effects of vildagliptin (50 or 100 mg daily) with placebo as an add‐on therapy to pioglitazone (45 mg daily) in 463 patients with T2DM inadequately controlled by prior TZD monotherapy. Between‐treatment comparisons of efficacy parameters were made by analysis of covariance model. Results: The adjusted mean change (AMΔ) in haemoglobin A_1c from baseline to endpoint was −0.8 ± 0.1% (p = 0.001 vs. placebo) and −1.0 ± 0.1% (p < 0.001 vs. placebo), respectively, in patients receiving vildagliptin 50 or 100 mg daily. Relative to baseline, vildagliptin added to pioglitazone also reduced fasting plasma glucose (FPG) (AMΔ FPG =−0.8 ± 0.2 mmol/l and −1.1 ± 0.2 mmol/l; not significant (NS) vs. placebo) and postprandial glucose (PPG) [AMΔ PPG =−1.9 ± 0.6 mmol/l and −2.6 ± 0.6 mmol/l (p = 0.008 vs. placebo)] for 50 and 100 mg daily respectively. Relative to placebo, both doses of vildagliptin significantly increased the insulin secretory rate/glucose by more than threefold. The overall incidence of adverse events (AEs) was 55.5, 50.0 and 48.7% in patients receiving vildagliptin 50 mg, 100 mg daily or placebo respectively. Serious AEs were experienced by 6.8, 1.3 and 5.7% of patients receiving vildagliptin 50 mg, 100 mg daily or placebo respectively. Mild hypoglycaemia was reported by 0, 0.6 and 1.9% of patients, respectively, receiving vildagliptin 50 mg, 100 mg daily or placebo. Conclusion: Vildagliptin is effective and well tolerated when added to a maximum dose of pioglitazone, without increasing the risk of hypoglycaemia.