Canagliflozin: a sodium glucose co-transporter 2 inhibitor for the treatment of type 2 diabetes mellitus
Canagliflozin: a sodium glucose co-transporter 2 inhibitor for the treatment of type 2 diabetes mellitus
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DOI：
10.1111/nyas.12852
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发表时间：
2015-01-01
期刊：
影响因子：
--
通讯作者：
Demarest, Keith
中科院分区：
文献类型：
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作者：
Rosenthal, Norm;Meininger, Gary;Demarest, Keith
钠葡萄糖协同转运蛋白2（SGLT 2）抑制剂卡格列净是成人2型糖尿病（T2 DM）的一种新型治疗选择。在高血糖患者中，SGLT 2抑制剂通过降低葡萄糖肾阈值（RTC;）和增加尿糖排泄（UGE）降低血糖水平。UGE增加还与轻度渗透性利尿和净热量损失有关，这可能导致体重和血压（BP）下降。在临床前和I/II期研究取得令人鼓舞的结果后，在一项综合III期开发项目中，在超过10，000例接受各种背景治疗的T2 DM患者中评价了卡格列净的疗效和安全性。在长达2年的研究中，与安慰剂和活性对照药物相比，卡格列净改善了血糖控制，并降低了体重和BP。卡格列净的耐受性通常良好，与作用机制相关的不良事件（AE）发生率较高，包括生殖器支原体感染和与渗透性利尿相关的AE。临床前和临床研究的结果使卡格列净成为美国批准的第一种SGLT 2抑制剂，并支持卡格列净作为广泛的T2 DM患者的安全有效的治疗选择。
The sodium glucose co-transporter 2 (SGLT2) inhibitor canagliflozin is a novel treatment option for adults with type 2 diabetes mellitus (T2DM). In patients with hyperglycemia, SGLT2 inhibition lowers plasma glucose levels by reducing the renal threshold for glucose (RTC;) and increasing urinary glucose excretion (UGE). Increased UGE is also associated with a mild osmotic diuresis and net caloric loss, which can lead to reductions in body weight and blood pressure (BP). After promising results from preclinical and phase I/II studies, the efficacy and safety of canagliflozin was evaluated in a comprehensive phase III development program in over 10,000 patients with T2DM on various background therapies. Canagliflozin improved glycemic control and provided reductions in body weight and BP versus placebo and active comparators in studies of up to 2 years' duration. Canagliflozin was generally well tolerated, with higher incidences of adverse events (AEs) related to the mechanism of action, including genital mycotic infections and AEs related to osmotic diuresis. Results from the preclinical and clinical studies led canagliflozin to be the first -in -class SGLT2 inhibitor approved in the United States, and support canagliflozin as a safe and effective therapeutic option across a broad range of patients with T2DM.