Vildagliptin is a selective inhibitor of dipeptidyl peptidase-4, and prevents the rapid degradation of the incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide. Vildagliptin has been evaluated in > 4800 patients in nine Phase III studies in the range of 24 – 52 weeks in duration: four placebo- or active-controlled monotherapy trials that enrolled drug-naive patients; four add-on studies in which vildagliptin was added to a stable regimen of either metformin, a sulfonylurea, a thiazolidinedione or insulin; and a study in which an initial combination of vildagliptin plus pioglitazone in drug-naive patients was evaluated. Across studies, vildagliptin was effective in reducing HbA_1c, had a low risk of hypoglycemia and was weight-neutral and well tolerated.