Vildagliptin is a potent and selective inhibitor of dipeptidyl peptidase-4 (DPP-4), the enzyme responsible for the rapid degradation of circulating glucagon-like peptide-1. Mechanistic studies have shown that vildagliptin improves islet function in patients with type 2 diabetes (T2DM) by increasing both α- and β-cell responsiveness to glucose [1,2]. In phase II studies, vildagliptin was shown to decrease haemoglobin A1c (HbA1c) when given as monotherapy [3,4] or when added to metformin , and preclinical work with vildagliptin and pioglitazone suggested that the effects of this DPP-4 inhibitor would be complementary to those of a thiazolidinedione (TZD) . However, the efficacy and tolerability of vildagliptin combined with a TZD in patients with T2DM remain to be established.
Therefore, the present 24-week, multicentre, randomized, controlled clinical trial was conducted to ascertain the efficacy and tolerability of vildagliptin (50 or 100 mg daily) added to a maximum dose of pioglitazone (45 mg daily) in patients with T2DM inadequately controlled with TZD monotherapy. Mechanistic aspects were also explored during standard meal tests conducted in a subset of patients.