Different doses of imeglimin for management of type 2 diabetes mellitus: a systematic review, meta-analysis, and meta-regression of randomized clinical trials

A new medication for type 2 diabetes mellitus (T2DM) called imeglimin can target all three organs involved in the pathogenesis of DM, namely the liver, skeletal muscles, and pancreas. This research seeks to examine the most efficacious and safe dose of imeglimin for the management of T2DM.
Using particular keywords, we searched the CENTRAL, Medline, Scopus, and ClinicalTrials.gov databases for pertinent literature. The results of continuous variables were pooled into the mean difference (MD) and dichotomous variables into odds ratio (OR) along with their 95% confidence intervals (95% CI) using fixed-effect models.
Our pooled analysis revealed that imeglimin 1000 mg twice daily [MD −0.90% p < 0.00001] and 1500 mg twice daily [MD −0.84% p = 0.0003] as monotherapy was associated with a higher reduction in the HbA1c compared to placebo. This superiority was still maintained when given as combination therapy. Regrettably, there was an observed escalation in gastrointestinal AEs as the dosage of imeglimin was raised, despite the absence of a corresponding improvement in its efficacy in decreasing HbA1c levels.
Our study suggests that imeglimin 1000 mg twice daily may offer the most optimum therapeutic effects for glycemic control without compromising its safety profiles.

一款针对2型糖尿病（type 2 diabetes mellitus, T2DM）的新型药物依美格列净（imeglimin）可靶向糖尿病发病机制中涉及的全部三大器官，即肝脏、骨骼肌与胰腺。本研究旨在探究依美格列净用于2型糖尿病管理的最优有效且安全的给药剂量。

研究采用特定关键词，对CENTRAL、Medline、Scopus及ClinicalTrials.gov数据库中的相关文献进行检索。本研究采用固定效应模型，将连续变量的研究结果合并为均数差（mean difference, MD），将二分类变量的研究结果合并为比值比（odds ratio, OR）及其95%置信区间（95% confidence interval, 95% CI）。

合并分析结果显示，依美格列净1000mg每日两次[均数差−0.90%，p<0.00001]及1500mg每日两次[均数差−0.84%，p=0.0003]作为单药治疗时，相较于安慰剂，可更显著地降低糖化血红蛋白（HbA1c）水平；该治疗优势在联合用药方案中同样得以保持。遗憾的是，随着依美格列净给药剂量升高，胃肠道不良事件（adverse events, AEs）的发生率有所上升，但其降低HbA1c的疗效并未出现相应提升。

本研究表明，依美格列净1000mg每日两次或许可为血糖控制提供最优的治疗效果，且不会损害其安全性。