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 (AM Delta) 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) (AM Delta FPG =-0.8 +/- 0.2 mmol/l and -1.1 +/- 0.2 mmol/l; not significant (NS) vs. placebo) and postprandial glucose (PPG) [AM Delta 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.
Trial registration: ClinicalTrials.gov NCT00099853.