Department of Clinical Pharmacology, Bispebjerg Hospital, University of Copenhagen , Copenhagen, Denmark.
Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen , Hellerup, Denmark.
Expert Opin Pharmacother. 2020 Jun;21(8):871-882. doi: 10.1080/14656566.2020.1729123. Epub 2020 Feb 28.
With the rising prevalence of type 2 diabetes (T2D), there is a substantial interest in novel, glucose-lowering drugs that may complement existing treatment options. Imeglimin is an oral antidiabetic agent currently in clinical development.
This review is based on a literature search using PubMed and Embase including all published manuscripts and presentations concerning imeglimin. Supplementary information was retrieved from the manufacturer's official webpage. Preclinical and clinical data are summarized with a focus on mechanisms of action as well as clinical efficacy and safety in T2D.
Imeglimin's mode of action seems to be improved mitochondrial function in pancreatic beta cells leading to improved insulin secretion and lowering of plasma glucose levels. In clinical trials of up to 24 weeks, imeglimin in doses of 1,000-1,500 mg twice daily conferred modest reductions in glycates hemoglobin A1c of 6-11 mmol/mol (0.5-1.0%) (placebo-adjusted) as a monotherapy and 7 mmol/mol (0.6%) as an add-on therapy to metformin or sitagliptin in patients with T2D. Reported adverse effects were mainly gastrointestinal discomfort. The position of imeglimin among other pharmacotherapies in the treatment of T2D will be determined based on future studies more clearly outlining the safety and long-term cardiovascular effects.
AUC: area under the curve; BID: twice daily; DPP-4: dipeptidyl peptidase 4; GLP-1R: glucagon-like peptide-1 receptor; HbA1c: glycated hemoglobin A1c; HFHSD: high-fat high-sucrose diet; OAD: oral antidiabetic; OD: once daily; OGTT: oral glucose tolerance test; PPAR-γ: peroxisome proliferator-activated receptor gamma; PTP: permeability transition pore; SGLT-2: sodium-glucose transport protein 2; STZ: streptozotocin; T2D: type 2 diabetes.
随着 2 型糖尿病（T2D）患病率的上升，人们对新型降糖药物产生了浓厚的兴趣，这些药物可能是现有治疗选择的补充。伊格列净是一种正在临床开发中的口服抗糖尿病药物。
本综述基于对 PubMed 和 Embase 的文献检索，包括所有关于伊格列净的已发表文献和报告。补充信息从制造商的官方网页中检索。总结了其作用机制以及在 T2D 中的临床疗效和安全性的临床前和临床数据。
伊格列净的作用机制似乎是改善胰岛β细胞的线粒体功能，从而改善胰岛素分泌并降低血糖水平。在长达 24 周的临床试验中，伊格列净的剂量为 1000-1500mg，每日两次，作为单药治疗可使糖化血红蛋白 A1c 降低 6-11mmol/mol（0.5-1.0%）（安慰剂校正），作为二甲双胍或西格列汀的附加疗法可使糖化血红蛋白 A1c 降低 7mmol/mol（0.6%）。报告的不良反应主要是胃肠道不适。伊格列净在 T2D 治疗中的其他药物治疗中的地位将根据未来的研究来确定，这些研究将更清楚地阐明其安全性和长期心血管影响。
AUC：曲线下面积；BID：每日两次；DPP-4：二肽基肽酶 4；GLP-1R：胰高血糖素样肽-1 受体；HbA1c：糖化血红蛋白 A1c；HFHSD：高脂肪高蔗糖饮食；OAD：口服抗糖尿病药物；OD：每日一次；OGTT：口服葡萄糖耐量试验；PPAR-γ：过氧化物酶体增殖物激活受体γ；PTP：通透性转换孔；SGLT-2：钠-葡萄糖转运蛋白 2；STZ：链脲佐菌素；T2D：2 型糖尿病。
