853-P: Efficacy and Safety of HD-6277, a Novel GPR40 Agonist, in Patients with Type 2 Diabetes—A Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, Multicenter Phase 2 Trial

Objective: To assess the efficacy and safety of HD-6277, the first candidate of GPR40 in a new oral antidiabetic agent, in Adult Patients With Inadequate Control of Type 2 Diabetes Mellitus (T2DM)

Research Design & Methods: A double-blind, randomized, placebo-controlled phase 2 trial recruited 112 participants aged ≥ 20 years with T2DM with HbA1c between 7.0% and 10.0% while on diet and exercise alone for at least 8 weeks prior to screening. Parallel-group, randomized trial of HD-6277 50mg and 100mg group versus placebo were assigned for 12 weeks. The primary outcome was change in HbA1c at week 12 from baseline. Secondary outcomes included proportion of patients achieving HbA1c less than 7.0%, change in fasting plasma glucose(FPG), Changes in blood levels of post-meal glucose, insulin, glycoalbumin(GA), and C-peptide at week 12. In addition, changes in fasting lipid parameters, weight, GA/HbA1c ratio, HOMA (Homeostasis Model Assessment) β, and CD 36 were evaluated as exploratory endpoints.

Results: At week 12, compared to the placebo group, HD-6277 50mg and 100mg resulted in a statistically significant reduction of HbA1c levels by -0.73(95% CI -1.11, -0.35), p=0.0002 and -0.85 (95% CI -1.21, -0.50), P<0.0001, respectively. No significant increase in treatment-related adverse events was observed for HD-6277. Furthermore, significant improvements in FPG and GA levels were confirmed in the HD-6277 administration group compared to the placebo.

Conclusion: HD-6277 50mg and 100 mg improved glycaemic control in patients with T2DM inadequately controlled with diet and exercise, as shown by significant changes in HbA1c and FPG. The treatment with HD-6277 appeared to be safe and well tolerated. A GPR40 agonist represents a potential new treatment option for T2DM.