A randomized, double-blind, placebo-controlled, phase II clinical trial to investigate the efficacy and safety of oral DA-1229 in patients with type 2 diabetes mellitus who have inadequate glycaemic control with diet and exercise

BACKGROUND: DA-1229 is a novel, potent and selective dipeptidyl peptidase-4 (DPP-IV) inhibitor that is orally bioavailable. We aimed to evaluate the optimal dose, efficacy and safety of DA-1229, in Korean subjects with type 2 diabetes mellitus suboptimally controlled with diet and exercise. METHODS: We enrolled 158 patients (mean age, 53 years and a mean BMI, 25.6 kg/m(2)). The mean baseline fasting plasma glucose level, HbA1c and duration of diabetes were 8.28 mmol/L, 7.6% (60 mmol/mol) and 3.9 years, respectively. After 2 or 6 weeks of an exercise and diet program followed by 2 weeks of a placebo period, the subjects were randomized into one of four groups for a 12-week active treatment period: placebo, 2.5, 5 or 10 mg of DA-1229. RESULTS: All three doses of DA-1229 significantly reduced HbA1c from baseline compared to the placebo group (−0.09 in the placebo group vs. −0.56, −0.66 and −0.61% in 2.5, 5 and 10-mg groups, respectively) but without any significant differences between the doses. Insulin secretory function, as assessed by homeostasis model assessment β-cell, the insulinogenic index, 2-h oral glucose tolerance test (OGTT) C-peptide and post-OGTT C-peptide area under the curve (AUC)(0–2h,) significantly improved with DA-1229 treatment. The incidence of adverse events was similar between the treatment groups and DA-1229 did not affect body weight or induce hypoglycaemic events. CONCLUSIONS: DA-1229 monotherapy (5 mg for 12 weeks) improved HbA1c, fasting plasma glucose level, OGTT results and β-cell function. This drug was well tolerated in Korean subjects with type 2 diabetes mellitus. © 2014 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons, Ltd. DA-1229 is a novel, potent and selective DPP-IV inhibitor that is orally bioavailable. In a pharmacodynamic study, more than 80% of DPP-IV was inhibited by a single dose of 5 mg or higher of DA-1229, and this level of inhibition was maintained for at least 24 h after a single dose of 10 mg or higher of DA-1229. This phase II clinical trial was designed to evaluate the efficacy and safety of oral DA-1229 and to determine the optimal dose to use for a phase III clinical study in Korean subjects with type 2 diabetes.