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).
ABSTRACT
UNLABELLED: Aims/Introduction: Patients with type 2 diabetes mellitus often require treatment with more than one oral antihyperglycemic agent to achieve their glycemic goal. The present study was carried out to assess the efficacy and safety of sitagliptin as add-on therapy in Japanese patients with type 2 diabetes mellitus inadequately controlled (HbA1c ≥ 6.9% and <10.4%) on pioglitazone monotherapy (15-45 mg/day). MATERIALS AND METHODS: In the initial 12-week, double-blind treatment period, patients were randomized (1:1) to sitagliptin 50 mg/day (n = 66) or placebo (n = 68), followed by a 40-week open-label treatment period in which all patients received sitagliptin 50 mg/day that could have been increased to 100 mg/day for patients meeting predefined glycemic parameters. RESULTS: After 12 weeks, mean changes from baseline in HbA1c (the primary end-point), fasting plasma glucose and 2-h post-meal glucose were -0.8%, -0.9 mmol/L and -2.7 mmol/L, respectively, in the sitagliptin group compared with placebo (all P < 0.001). The incidence of adverse experiences during the double-blind treatment period was similar in both treatment groups, and the incidences of hypoglycemia and gastrointestinal adverse experiences were low. In the open-label period, improvements in glycemic parameters with sitagliptin treatment were maintained and sitagliptin was generally well tolerated. CONCLUSIONS: Sitagliptin as add-on therapy provided significant improvements in glycemic parameters and was well tolerated in Japanese patients with type 2 diabetes mellitus inadequately controlled on pioglitazone monotherapy. This trial was registered with ClinicalTrials.gov (no. NCT00372060). (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00120.x, 2011).
