Imeglimin: Current Development and Future Potential in Type 2 Diabetes.
Imeglimin: Current Development and Future Potential in Type 2 Diabetes.
复制标题
DOI：
10.1007/s40265-020-01434-5
复制
发表时间：
2021-03
期刊：
影响因子：
11.5
通讯作者：
Perry RJ
中科院分区：
文献类型：
--
作者：
Konkwo C;Perry RJ
Imeglimin是一种新型药物“glimins”中的第一种，用于治疗2型糖尿病（T2D）。本文综述了其作用机制及其在T2D治疗领域的背景。多种啮齿动物模型的临床前数据详细说明了对线粒体的显著影响，特别是改善了线粒体生物能量学。这包括有利于复合物II和复合物III代谢的变化，这是一种可能促进脂肪酸氧化增加的机制，导致在这些小鼠中观察到的肝脏脂质蓄积减少。在体外和体内试验中，Imeglimin也显示出增加肌肉葡萄糖摄取和减少肝脏葡萄糖产生。虽然研究也表明imeglimin可以显著改善胰岛素分泌和减少β细胞死亡，但其生理作用是否纯粹依赖于胰岛素的问题仍不清楚。早期的临床前研究已经显示出代谢综合征大鼠的心脏和肾功能改善的证据，这是大多数目前可用的T2D药物所不具有的效果。伊格列明在人体中的临床研究显示，伊格列明可增加胰岛素分泌，沿着空腹血糖和血红蛋白A1 c降低。其观察到的疗效与目前可用的药物二甲双胍和西格列汀相当，并且当与任一药物联合给药时增加。与慢性肾脏疾病患者中报告的良性安全性特征一起考虑时，imeglimin显示出真正的前景，可为T2D治疗提供一种新的机制，并可能在更大，更全面的患者人群中应用。
Imeglimin is the first of a new class of drugs, “glimins,” developed for the treatment of type 2 diabetes (T2D). This review highlights its mechanism of action, and its context in the field of T2D treatment. Preclinical data in multiple rodent models detail significant effects on mitochondria, particularly improved mitochondrial bioenergetics. This includes changes favoring complex II and complex III metabolism, a mechanism potentially promoting increased fatty acid oxidation, leading to the decrease in hepatic lipid accumulation observed in these mice. Imeglimin was also shown to increase muscle glucose uptake and decrease hepatic glucose production both in vitro and in vivo. Though studies have also shown imeglimin to significantly improve insulin secretion and decrease beta cell death, the question of whether its physiologic effects are purely insulin-dependent is still unclear. Early preclinical studies have shown evidence for improvements in cardiac and renal function in rats with metabolic syndrome, effects not conferred by most currently available T2D drugs. Clinical studies of imeglimin in humans have shown increased insulin secretion, along with decreased fasting plasma glucose and hemoglobin A1c. Its observed efficacy was comparable to currently available agents metformin and sitagliptin, and was increased when given in combination with either agent. When considered alongside its benign safety profile reported in patients with chronic kidney disease, imeglimin shows true promise to provide a novel mechanism for T2D treatment with potential application in a larger, more comprehensive patient population.
登录
查看更多内容
影响因子：
7.7
作者：
Vial, Guillaume;Chauvin, Marie-Agnes;Rieusset, Jennifer
通讯作者：
Rieusset, Jennifer
影响因子：
16.2
作者：
Fouqueray, Pascale;Pirags, Valdis;Bailey, Clifford J.
通讯作者：
Bailey, Clifford J.
DOI：
10.4172/2155-6156.1000126
发表时间：
2011-05-01
期刊：
JOURNAL OF DIABETES & METABOLISM
影响因子：
--
作者：
Fouqueray, Pascale;Leverve, Xavier;Bozec, Sophie
通讯作者：
Bozec, Sophie
影响因子：
3.1
作者：
Fakharnia, Farinoosh;Khodagholi, Fariba;Ahmadiani, Abolhassan
通讯作者：
Ahmadiani, Abolhassan
影响因子：
3.7
作者：
Giaime E;Yamaguchi H;Gautier CA;Kitada T;Shen J
通讯作者：
Shen J