Efficacy and Safety of Imeglimin Monotherapy Versus Placebo in Japanese Patients With Type 2 Diabetes (TIMES 1): A Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, Multicenter Phase 3 Trial

<b>Objective.</b> The aim of this study was to investigate the efficacy and safety of imeglimin, the first in a new class of oral antidiabetic agent, in Japanese patients with type 2 diabetes. <p><b>Research Design and Methods.</b> This was a double-blind, randomized, parallel-group, placebo-controlled phase 3 trial in 30 sites in Japan. Eligible participants were individuals aged 20 years or older with type 2 diabetes treated with diet and exercise stable for at least 12 weeks prior to screening and an HbA1c of 7.0%-10.0% (53-86mmol/mol). Patients were randomly assigned (1:1) to either oral imeglimin (1000 mg BID), or matched placebo for 24 weeks. Investigators, participants and the sponsor of the study remained blinded throughout the trial. The primary endpoint was the change in mean HbA1c from baseline to week 24, and the key secondary endpoints were the percentage of responders (according to two definitions) at week 24. </p> <p><b>Results.</b> Between 26^th December 2017 and 1^st February 2019, we randomly assigned 106 patients to imeglimin 1000 mg BID and 107 patients to placebo. Compared with placebo, adjusted mean difference in change from baseline HbA1c at week 24 was -0.87% (95% CI -1.04 to -0.69 / -9.5mmol/mol (95%CI -11.4 to -7.5) (p<0.0001). Forty-seven (44.3%) patients reported at least one adverse event in the imeglimin group versus 48 (44.9%) in the placebo group. </p> <p><b>Conclusions.</b> Imeglimin significantly improved HbA1c in Japanese patients with type 2 diabetes compared with placebo, and showed a similar safety profile to placebo, representing a potential new treatment option for this population. </p>