Efficacy and tolerability of sitagliptin, a dipeptidyl peptidase-4 inhibitor, were assessed in Japanese patients with type 2 diabetes. In a multicenter, double-blind, randomized, placebo-controlled trial in Japan, 151 patients with inadequate glycemic control [HbA(1c) > or =6.5% to <10%, fasting plasma glucose (FPG) > or =126 to < or =240 mg/dL] were randomized to once-daily sitagliptin 100mg or placebo for 12 weeks. After 12 weeks, the least squares (LS) mean change from baseline HbA(1c) was -0.65% (95% CI: -0.80, -0.50) with sitagliptin versus 0.41% (0.26, 0.56) with placebo [between-group difference=-1.05% (-1.27, -0.84); p<0.001]. LS mean change from baseline FPG was -22.5mg/dL (95% CI: -28.0, -17.0) with sitagliptin versus 9.4 mg/dL (3.9, 14.9) with placebo [between-group difference=-31.9 mg/dL (95% CI: -39.7,-24.1); p<0.001]. More patients achieved HbA(1c) <7% or <6.5% with sitagliptin than with placebo (p<0.001). Following a meal tolerance test, 2-h postprandial glucose was significantly reduced with sitagliptin relative to placebo. Clinical and laboratory adverse experiences were similar between treatments, with no reported hypoglycemia adverse events with sitagliptin. Body weight was unchanged relative to baseline in the sitagliptin group (-0.1 kg), but significantly (p<0.01) different relative to the placebo group (-0.7 kg). In this study, once-daily sitagliptin 100mg for 12 weeks improved fasting and postprandial glycemic control and was generally well tolerated in Japanese patients with type 2 diabetes.