multicenter, randomized, placebo‐controlled, double‐blind phase II trial evaluating the optimal dose, efficacy and safety of LC 15‐0444 in patients with type 2 diabetes

Aim: The objective of this study was to evaluate the optimal dose, efficacy and safety of a novel dipeptidyl peptidase‐4 (DPP‐IV) inhibitor, LC15‐0444, in Korean subjects with type 2 diabetes mellitus treated by diet and exercise. Methods: This study was a double‐blind, randomized, multicenter and parallel‐group, dose‐range finding study. We enrolled 145 patients (91 men and 54 women) with a median age of 53 years and a median body mass index of 25.1 kg/m². The median baseline fasting plasma glucose (FPG) was 8.1 mmol/l, the median HbA1c was 7.9% and the median time since the diagnosis of diabetes was 3 years. After 2 weeks of an exercise/diet programme followed by 2 weeks of a placebo period, the subjects were randomized to one of the four following groups for a 12‐week active treatment period: placebo and 50, 100 or 200 mg of LC15‐0444. Results: All three doses of LC15‐0444 significantly reduced the HbA1c from baseline compared to the placebo group (−0.06 vs. −0.98, −0.74 and −0.78% in the placebo and 50, 100 and 200 mg groups, respectively), without a significant difference between the doses. Subjects with a higher baseline HbA1c (≥8.5%) had a greater reduction in HbA1c. Insulin secretory function, as assessed using homeostasis model assessment‐beta cell, C‐peptide and the insulinogenic index, improved significantly with LC15‐0444 treatment. Insulin sensitivity, as assessed using homeostasis model assessment‐insulin resistance, also improved significantly after 12 weeks of treatment. The 50 and 200 mg groups had significantly reduced total cholesterol and low‐density lipoprotein cholesterol levels at 12 weeks compared to the placebo group. No dosage of LC15‐0444 affected weight or waist circumference. The incidences of adverse events were similar in all study subjects. Conclusions: LC15‐0444 monotherapy (50 mg for 12 weeks) improved the HbA1c, FPG level, oral glucose tolerance test results, β‐cell function and insulin sensitivity measures, and was well tolerated in Korean subjects with type 2 diabetes.