Abstract
AIMS/INTRODUCTION: The efficacy and safety of sitagliptin, a highly selective dipeptidyl peptidase-4 inhibitor, when added to metformin monotherapy was examined in Japanese patients with type 2 diabetes. MATERIALS AND METHODS: In this 52-week, add-on to metformin study, 149 patients were randomly assigned to receive sitagliptin 50 mg or placebo once daily in a double-blind fashion for 12 weeks. Thereafter, all patients who completed the double-blind period of the study received open-label sitagliptin 50 mg once daily for 40 weeks, with the investigator option of increasing sitagliptin to 100 mg once daily for patients who met predefined glycemic thresholds. RESULTS: After 12 weeks of treatment, the mean change from baseline in glycated hemoglobin (HbA1c) significantly decreased with sitagliptin relative to placebo (between-group difference [95% confidence interval] = -0.7% [-0.9 to -0.5] P < 0.001). At week 12, the mean changes in 2-h post-meal glucose (-2.6 mmol/L [-3.5 to -1.7]) and fasting plasma glucose (-1.0 mmol/L [-1.3 to -0.6]) also decreased significantly with sitagliptin relative to placebo (P < 0.001 for both). Significant improvements from baseline in glycemic control were also observed in the open-label period through to week 52. There were no differences between treatment groups in the incidence of adverse events (AEs), including hypoglycemia and predefined gastrointestinal AEs (nausea, vomiting and diarrhea) during the double-blind period, with similar findings in the open-label period. CONCLUSIONS: Over a period of 52 weeks, the addition of sitagliptin once-daily to ongoing metformin therapy was efficacious and generally well tolerated in Japanese patients with type 2 diabetes. This trial was registered with ClinicalTrials.gov (no. NCT00363948).