Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University, Nagakute, Aichi 480-1195, Japan.
Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Gifu 503-8502, Japan.
Int J Mol Sci. 2020 Jul 13;21(14):4939. doi: 10.3390/ijms21144939.
Type 2 diabetes (T2D) is associated with diabetic nephropathy as well as nonalcoholic steatohepatitis (NASH), which can be called "diabetic hepatopathy or diabetic liver disease". NASH, a severe form of nonalcoholic fatty disease (NAFLD), can sometimes progress to cirrhosis, hepatocellular carcinoma and hepatic failure. T2D patients are at higher risk for liver-related mortality compared with the nondiabetic population. NAFLD is closely associated with chronic kidney disease (CKD) or diabetic nephropathy according to cross-sectional and longitudinal studies. Simultaneous kidney liver transplantation (SKLT) is dramatically increasing in the United States, because NASH-related cirrhosis often complicates end-stage renal disease. Growing evidence suggests that NAFLD and CKD share common pathogenetic mechanisms and potential therapeutic targets. Glucagon-like peptide 1 (GLP-1) receptor agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors are expected to ameliorate NASH and diabetic nephropathy/CKD. There are no approved therapies for NASH, but a variety of drug pipelines are now under development. Several agents of them can also ameliorate diabetic nephropathy/CKD, including peroxisome proliferator-activated receptors agonists, apoptosis signaling kinase 1 inhibitor, nuclear factor-erythroid-2-related factor 2 activator, C-C chemokine receptor types 2/5 antagonist and nonsteroidal mineral corticoid receptor antagonist. This review focuses on common drug pipelines in the treatment of diabetic nephropathy and hepatopathy.
2 型糖尿病（T2D）与糖尿病肾病以及非酒精性脂肪性肝炎（NASH）有关，后者也被称为“糖尿病肝或糖尿病肝病”。NASH 是一种严重的非酒精性脂肪性疾病（NAFLD），有时可进展为肝硬化、肝细胞癌和肝功能衰竭。与非糖尿病患者相比，T2D 患者的肝脏相关死亡率更高。根据横断面和纵向研究，NAFLD 与慢性肾脏病（CKD）或糖尿病肾病密切相关。由于 NASH 相关的肝硬化常合并终末期肾病，美国的肝肾联合移植（SKLT）数量正在大幅增加。越来越多的证据表明，NAFLD 和 CKD 具有共同的发病机制和潜在的治疗靶点。胰高血糖素样肽 1（GLP-1）受体激动剂和钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂有望改善 NASH 和糖尿病肾病/CKD。目前尚无治疗 NASH 的获批药物，但目前正在开发多种药物管线。其中一些药物也可改善糖尿病肾病/CKD，包括过氧化物酶体增殖物激活受体激动剂、凋亡信号激酶 1 抑制剂、核因子-红细胞 2 相关因子 2 激活剂、C-C 趋化因子受体 2/5 拮抗剂和非甾体类盐皮质激素受体拮抗剂。本文重点介绍了治疗糖尿病肾病和肝病的常见药物管线。
