钠-葡萄糖共转运蛋白2抑制剂卡格列净在2型糖尿病治疗中的新进展

doi:10.5246/jcps.2022.08.049

中国药学(英文版) ›› 2022, Vol. 31 ›› Issue (8): 569-588.DOI: 10.5246/jcps.2022.08.049

• 【综述】 • 下一篇

钠-葡萄糖共转运蛋白2抑制剂卡格列净在2型糖尿病治疗中的新进展

付颖¹^,², 刘思默¹^,², 马燕¹^,², 吴南楠¹^,²^,^*()

1. 首都医科大学附属北京潞河医院内分泌代谢与免疫性疾病中心, 北京 101149
2. 糖尿病防治研究北京市重点实验室, 北京 101149

收稿日期:2022-04-21 修回日期:2022-05-06 接受日期:2022-05-24 出版日期:2022-09-03 发布日期:2022-09-03
通讯作者: 吴南楠
作者简介:
+ Tel.: +86-10-69543901-6906, E-mail: 15010076018@163.com
基金资助:
Beijing Excellent Talents Training Assistance (Grant No. 2017000082595G244) and the Health and Research Bureau of Tongzhou District (Grant No. TWKY-2016-QN-01-58).

Canagliflozin, an inhibitor of sodium-glucose co-transporter 2, advances in the treatment of type 2 diabetes

Ying Fu¹^,², Simo Liu¹^,², Yan Ma¹^,², Nannan Wu¹^,²^,^*()

1 Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital, Capital Medical University, Beijing 101149, China
2 Beijing Key Laboratory of Diabetes Research and Care, Beijing 101149, China

Received:2022-04-21 Revised:2022-05-06 Accepted:2022-05-24 Online:2022-09-03 Published:2022-09-03
Contact: Nannan Wu

摘要/Abstract

摘要：

卡格列净是一种钠-葡萄糖共转运蛋白2抑制剂。卡格列净的重要机制之一是阻断肾小球近曲小管对葡萄糖的重吸收, 另一机制可能是减少炎性细胞因子表达的单核细胞和巨噬细胞。FDA也证明它可以用于2型糖尿病的治疗。在此, 我们总结了有关卡格列净对健康个体和代谢相关疾病(如1型和2型糖尿病、肥胖、一些心血管和肾脏疾病)的发表和临床证据。据报道, 该药物在调节2型糖尿病患者体重、降低心力衰竭、低血糖和中风风险方面具有潜在优势。一些体外和动物实验也表明, 该药物对癌症治疗有良好的效果。然而, 一些病例报道和实验也显示卡格列净的副作用, 如截肢、骨折、胰腺炎等, 但其作用机制尚不清楚。总的来说, 卡格列净通过降低肾衰竭、心血管疾病和中风的风险, 对2型糖尿病的管理有良好的效果。但作为一种新药, 卡格列净还需要进行更多的临床试验和实验。

关键词: 钠-葡萄糖共转运蛋白2抑制剂, 卡格列净, 糖尿病

Abstract:

Canagliflozin (CANA) is a sodium-glucose co-transporter 2 inhibitor. One of the important mechanisms of CANA is the inhibitory effect on the glucose uptake in the proximal tubule of the nephron, and the other mechanism can be the reduction of inflammatory cytokine expression monocytes and macrophages. It is proved by FDA for the management of type 2 diabetes. In the present work, we summarized the publication and clinical evidence of the CANA on healthy individuals and those with related metabolic diseases, such as type 1 and 2 diabetes, obesity, or cardiovascular and kidney diseases. This drug has been reported to offer potential advantages in regulating body weight and reducing heart failure, hypoglycemia, and stroke risk in patients with type 2 diabetes. Some in vitro and animal experiments also show that this drug has good effects on cancer treatment. However, some case reports and experiments also show the side effect of CANA, such as amputation, fracture, and pancreatitis, while the mechanism is still unknown. Overall, CANA has a good effect on the management of type 2 diabetes by reducing the risk of kidney failure, cardiovascular diseases, and stroke. However, as a new drug, more clinical trials and experiments of CANA should be carried out in the future.

Key words: Sodium-glucose co-transporter 2 inhibitors, Canagliflozin, Diabetes mellitus

Supporting:

付颖, 刘思默, 马燕, 吴南楠. 钠-葡萄糖共转运蛋白2抑制剂卡格列净在2型糖尿病治疗中的新进展[J]. 中国药学(英文版), 2022, 31(8): 569-588.

Ying Fu, Simo Liu, Yan Ma, Nannan Wu. Canagliflozin, an inhibitor of sodium-glucose co-transporter 2, advances in the treatment of type 2 diabetes[J]. Journal of Chinese Pharmaceutical Sciences, 2022, 31(8): 569-588.

图/表 2

Figure 1. Illustration of the primary mechanisms of action of SGLT2 inhibitors. CANA inhibits the hyperglycemia-induced activation of the protein kinase C (PKC)-NAD(P)H oxidase pathway and increases the production of reactive oxygen species (ROS) and CANA can down-regulate the expression of β-catenin by promoting proteasome degradation of phosphorylated β-catenin, induce protein phosphatase 2A inactivation, and slow down the cell proliferation. There are some other functions of CANA in different cell types, and that can dysregulate the expressions of some inflammatory cytokines.

Table 1. The reported clinical trials of CANA.

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钠-葡萄糖共转运蛋白2抑制剂卡格列净在2型糖尿病治疗中的新进展

Canagliflozin, an inhibitor of sodium-glucose co-transporter 2, advances in the treatment of type 2 diabetes

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