Osonoi Takeshi, Shirabe Shinichiro, Saito Miyoko, Hosoya Mitsuru, Douguchi Satako, Ofuchi Kensuke, Katoh Makoto
Naka Kinen Clinic, Ibaraki, Japan.
Front Pharmacol. 2023 Jun 7;14:1205021. doi: 10.3389/fphar.2023.1205021. eCollection 2023.
Imeglimin is a novel type 2 diabetes (T2D) drug that is expected to improve mitochondrial function. In its phase 3 clinical trials in Japanese patients with T2D, the hemoglobin A1c (HbA1c) decrease following imeglimin administration was slow, reaching a plateau after 20-24 weeks of treatment. In general, the erythrocyte lifespan may be a factor when HbA1c shows an abnormal value. Therefore, this study will comparatively evaluate HbA1c and other markers of glycemic control in patients with T2D after imeglimin administration and also examine the effects of imeglimin on erythrocytes. This single-arm, open-label, prospective, exploratory study is designed to evaluate the divergence between HbA1c and glycoalbumin (GA) or 1,5-anhydroglucitol (1,5-AG) and the glycemic reduction rate in 30 patients with T2D with inadequate glycemic control when imeglimin 2,000 mg is administered for 6 months. In addition, we will examine the effect on erythrocytes, the presumed cause of this divergence. We will measure sustained glycemic variability using flash glucose monitoring and examine the relationship between changes in these indices and HbA1c. Moreover, because prolonged erythrocyte lifespan is a possible cause of falsely high HbA1c levels, erythrocyte lifespan, erythrocyte deformability, and hemoglobin concentration will be evaluated as effects of imeglimin on erythrocytes. Furthermore, if imeglimin has an ameliorative effect on erythrocyte deformability, it may improve peripheral arterial disease; thus, we will also evaluate the toe-brachial pressure index, a measure of this effect. In this study, if imeglimin administration results in diverging rates of hypoglycemic effect between HbA1c and GA or 1,5-AG and prolongs erythrocyte lifespan, GA and 1,5-AG, rather than HbA1c, will be considered appropriate measures of the hypoglycemic effect in the early stages of imeglimin administration. If imeglimin improves erythrocyte deformability, it may also be a new treatment strategy for peripheral arterial disease, a chronic complication of T2D. The study protocol was scientifically and ethically reviewed and approved by the Certified Clinical Research Review Board of Toho University (approval number: THU22002). The study protocol was registered in the Japan Registry of Clinical Trials (jRCT) in December 2022 (jRCTs031220489).
依美格列明是一种新型2型糖尿病（T2D）药物，有望改善线粒体功能。在针对日本T2D患者的3期临床试验中，服用依美格列明后糖化血红蛋白（HbA1c）的下降较为缓慢，治疗20 - 24周后达到平台期。一般来说，当HbA1c值异常时，红细胞寿命可能是一个影响因素。因此，本研究将比较评估依美格列明给药后T2D患者的HbA1c及其他血糖控制指标，并研究依美格列明对红细胞的影响。 这项单臂、开放标签、前瞻性探索性研究旨在评估30例血糖控制不佳的T2D患者在服用2000 mg依美格列明6个月时，HbA1c与糖化白蛋白（GA）或1,5 - 脱水葡萄糖醇（1,5 - AG）之间的差异以及降糖率。此外，我们将研究对红细胞的影响，这是这种差异的推测原因。我们将使用动态血糖监测来测量持续血糖变异性，并研究这些指标变化与HbA1c之间的关系。此外，由于红细胞寿命延长可能是HbA1c水平假性升高的原因，因此将评估红细胞寿命、红细胞变形性和血红蛋白浓度作为依美格列明对红细胞的影响。此外，如果依美格列明对红细胞变形性有改善作用，可能会改善外周动脉疾病；因此，我们还将评估反映这种作用的指标——趾臂压力指数。 在本研究中，如果服用依美格列明导致HbA1c与GA或1,5 - AG之间的降糖效果速率出现差异，并延长红细胞寿命，那么在依美格列明给药早期，GA和1,5 - AG而非HbA1c将被视为评估降糖效果的合适指标。如果依美格列明改善了红细胞变形性，它也可能成为T2D慢性并发症外周动脉疾病的一种新治疗策略。 该研究方案经过了东邦大学认证临床研究审查委员会的科学和伦理审查并获得批准（批准号：THU22002）。该研究方案于2022年12月在日本临床试验注册中心（jRCT）注册（jRCTs031220489）。
