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2 型糖尿病的新兴治疗方法:关注卡格列净。

Emerging treatments in type 2 diabetes: focus on canagliflozin.

机构信息

Department of Cardiology and Hypertension, Central Clinical Hospital, the Ministry of the Interior, Warsaw, Poland ; Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Poland.

Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Poland.

出版信息

Ther Clin Risk Manag. 2014 Aug 21;10:683-9. doi: 10.2147/TCRM.S39145. eCollection 2014.

Abstract

Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder, which affects more than 300 million people globally. The common effect of uncontrolled diabetes is the state of hyperglycemia, which results from beta-cell dysfunction as well as insulin resistance, which is accompanied with microvascular and macrovascular complications. As hyperglycemia defines diabetes, glycemic control is fundamental to the management of diabetes. Sodium glucose co-transporter 2 inhibitors (SGLT2) are a new group of oral antidiabetic medications that act by blocking the reabsorption of glucose, causing it to be excreted in the urine. Canagliflozin was the first SGLT2 inhibitor to be approved in the US by the Food and Drug Administration for the treatment and control of T2DM and on September 19, 2013, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Invokana(®). Canagliflozin is a SGLT2 inhibitor, which acts upon the proximal tubules of the kidneys and reduces the renal threshold for glucose. It is highly selective, binding 250 times more potently to SGLT2 than sodium glucose co-transporter 1 inhibitor. This action allows a higher amount of glucose to be excreted within the urine, causing the patient's plasma glucose level to be decreased and indirectly causing weight loss. Among the most common adverse events are hypoglycemia, headache, nausea, female genital and urinary tract infections, nasopharyngitis, and transient postural dizziness. Given its high efficacy in reducing hyperglycemia and good safety profile as either monotherapy or an add-on treatment to metformin, sulfonylureas, or insulin, canagliflozin seems to be a promising antihyperglycemic drug. Nevertheless, further large-scale and long-term studies should be conducted to evaluate the impact of canagliflozin on cardiovascular risk in T2DM patients.

摘要

2 型糖尿病(T2DM)是一种常见的代谢紊乱疾病,影响着全球超过 3 亿人。糖尿病失控的常见后果是高血糖状态,这是由β细胞功能障碍以及胰岛素抵抗引起的,同时伴有微血管和大血管并发症。由于高血糖定义了糖尿病,血糖控制是糖尿病管理的基础。钠-葡萄糖协同转运蛋白 2 抑制剂(SGLT2)是一类新型的口服降糖药物,通过阻断葡萄糖的重吸收,使其在尿液中排出。坎格列净是第一个被美国食品和药物管理局(FDA)批准用于治疗和控制 2 型糖尿病的 SGLT2 抑制剂,2013 年 9 月 19 日,欧洲药品管理局人用医药产品委员会(CHMP)发表积极意见,建议批准上市用于治疗 2 型糖尿病的药物 Invokana(®)。坎格列净是一种 SGLT2 抑制剂,作用于肾脏的近端小管,降低肾脏对葡萄糖的阈值。它具有高度选择性,与 SGLT1 抑制剂的结合力强 250 倍。这种作用使更多的葡萄糖在尿液中排出,导致患者的血浆葡萄糖水平降低,并间接导致体重减轻。最常见的不良反应包括低血糖、头痛、恶心、女性生殖道和尿路感染、鼻咽炎和短暂体位性头晕。鉴于其在降低高血糖方面的高疗效和良好的安全性,作为单药治疗或与二甲双胍、磺酰脲类或胰岛素联合治疗,坎格列净似乎是一种有前途的抗高血糖药物。然而,应该进行更大规模和长期的研究,以评估坎格列净对 2 型糖尿病患者心血管风险的影响。

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