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. RESEARCH DESIGN AND METHODSThis was a double-blind, randomized, parallel-group, placebo-controlled phase 3 trial in 30 sites in Japan. Eligible participants were individuals aged ‡20 years with type 2 diabetes treated with diet and exercise, stable for ‡12 weeks prior to screening, and whose HbA 1c was 7.0-10.0% (53-86 mmol/mol). Patients were randomly assigned (1:1) to either oral imeglimin (1,000 mg twice daily) or matched placebo for 24 weeks. Investigators, participants, and the sponsor of the study remained blinded throughout the trial. The primary end point was the change in mean HbA 1c from baseline to week 24, and the key secondary end point was the percentage of responders (according to two definitions) at week 24. RESULTSBetween 26 December 2017 and 1 February 2019, 106 and 107 patients were randomly assigned to treatment with imeglimin and placebo, respectively. Compared with placebo, the adjusted mean difference in change from baseline HbA 1c at week 24 was 20.87% (95% CI 21.04 to 20.69 [29.5 mmol/mol; 95% CI 211.4 to 27.5]; P < 0.0001). Forty-seven (44.3%) patients reported ‡1 adverse event in the imeglimin group versus 48 adverse events (44.9%) in the placebo group. CONCLUSIONSImeglimin significantly improved HbA 1c in Japanese patients with type 2 diabetes compared with placebo and had a similar safety profile to placebo. Imeglimin represents a potential new treatment option for this population.

Aims: To evaluate the efficacy and safety of imeglimin for up to 52 weeks as combination therapy with insulin in Japanese patients with type 2 diabetes.Materials and Methods: This double-blind, randomized, parallel-group phase 3 trial was performed at 35 sites in Japan. Eligible patients were individuals aged ≥20 years with type 2 diabetes and inadequate glycaemic control with insulin. Patients were randomly assigned (1:1) to either imeglimin (1000 mg twice daily) or matched placebo, in combination with insulin, for 16 weeks. In a subsequent 36-week, open-label extension period, all patients received imeglimin 1000 mg twice daily. The primary endpoint was change in mean glycated haemoglobin (HbA1c) from baseline to week 16.Results: In all, 108 and 107 patients were randomly assigned to treatment with imeglimin 1000 mg twice daily or placebo, respectively. Compared with placebo, the adjusted mean difference in change from baseline HbA1c at Week 16 was À0.60% (95% confidence interval [CI] À0.80 to À0.40; P < 0.0001). This decrease was sustained up to 52 weeks with a mean decrease of À0.64% (95% CI À0.82 to À0.46) versus baseline.The incidence of patients experiencing adverse events and serious adverse events was similar in the two treatment groups. The number of patients experiencing hypoglycaemia was similar in the two treatment groups. In patients receiving imeglimin, all hypoglycaemic events were mild in severity; no episodes required assistance.Conclusions: Imeglimin significantly improved HbA1c in Japanese patients with insufficiently controlled type 2 diabetes by insulin and had a similar safety profile to placebo. The efficacy of imeglimin on top of insulin was sustained for 52 weeks. Imeglimin represents a potential new treatment option for this population as add-on to insulin therapy.Caroline Reilhac and Julie Dubourg contributed equally to the manuscript.

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Intake of AQ and AS with a high fat meal resulted in (1) a statistically significant increase in blood levels of AQ and DSA which may affect the safety and tolerability of the study drugs and (2) a decrease in AS and DHA blood levels which may affect efficacy. These results suggest that the fixed-dose combination should not be administered with a high-fat meal.

Introduction:The aim of the present study was to evaluate the effect of 18-week monotherapy with imeglimin on glucose tolerance and on insulin secretion/sensitivity in type 2 diabetic (T2D) patients. Methods:The study was an 18-week, double-blind clinical trial in T2D subjects previously treated with stable metformin therapy and washed out for 4 weeks. Subjects were randomized 1:1 to receive a 1500 mg bid of imeglimin or placebo. The primary endpoint was the effect of imeglimin vs placebo on changes from baseline to week 18 in glucose tolerance (glucose area under the curve [AUC]) during a 3 h-glucose tolerance test [OGTT]). Secondary endpoints included glycaemic control and calculated indices of insulin secretion and sensitivity.Results: A total of 59 subjects were randomized, 30 receiving imeglimin and 29 receiving placebo. The study met its primary endpoint. Least squares (LS) mean difference between treatment groups (imeglimin -placebo) for AUC glucose from baseline to week 18 was −429.6 mmol/L•min (p = .001). Two-hour post-dose fasting plasma glucose was significantly decreased with LS mean differences of −1.22 mmol/L (p = .022) and HbA1c was improved with LS mean differences of −0.62% (p = .013).The AUC 0-180min ratio C-peptide/glucose [LS mean differences of 0.041 nmol/mmol (p < .001)] and insulinogenic index were significantly increased by imeglimin treatment. The increase in insulin secretion was associated with an increase in beta-cell glucose sensitivity. Additionally, the insulin sensitivity indices derived from the OGTT Stumvoll (p = .001) and Matsuda (not significant) were improved in the imeglimin group vs placebo. Imeglimin was well tolerated with 26.7% of subjects presenting at least one treatment-emergent adverse event versus 58.6% of subjects in the placebo group. Conclusions:Results are consistent with a mode of action involving insulin secretion as well as improved insulin sensitivity and further support the potential for imeglimin to improve healthcare in T2D patients.