Efficacy and Tolerability of Vildagliptin in Patients with Type 2 Diabetes Inadequately Controlled with Metformin Monotherapy

The aim of the study was to evaluate the efficacy and safety of vildagliptin added to metformin in patients with type 2 diabetes mellitus. A multicentre, double-blind, randomized, placebo-controlled, 24-week study in patients inadequately controlled with metformin (HbA(1c) 7.5-11%) was designed. Patients were randomized to vildagliptin (Galvus (R)) 100 mg given in the morning (AM), vildagliptin 100 mg given in the evening (PM), or placebo. The primary objective was to demonstrate that HbA(1c) reduction with once-daily vildagliptin 100 mg AM dosing is superior to placebo. Change from baseline to study endpoint in adjusted mean (SE) HbA(1c) improved significantly with vildagliptin AM dosing (-0.66 [0.11] versus 0.17% [0.11] with placebo; p <0.001). Subgroup analyses revealed that HbA(1c) reduction from baseline was greatest in those patients who had the highest baseline HbA(1c) levels. According to a predefined set of response criteria, the percentage of responder patients was significantly greater in the vildagliptin AM dosing group than in the placebo group for all responder definitions. Further analysis also revealed comparable efficacy between AM and PM dosing. Body weight remained generally stable in the combined vildagliptin group (+ 0.06 kg) and decreased with placebo (-0.69kg); the incidence of adverse events was similar with vildagliptin AM dosing and placebo (30.4 and 34.4%, respectively). Vildagliptin 100 mg given as a morning dose is an effective and well-tolerated treatment option in patients with type 2 diabetes mellitus inadequately controlled with metformin monotherapy, and is equally efficacious when given as either a morning or evening dose.