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钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂:满足2型糖尿病未满足需求的新型药物。

SGLT2 inhibitors: New medicines for addressing unmet needs in type 2 diabetes.

作者信息

Moses Robert G, Colagiuri Stephen, Pollock Carol

机构信息

Illawarra Diabetes Service, Clinical Trial and Research Unit, Illawarra Shoalhaven Local Health District,Wollongong, NSW, Australia.

Boden Institute of Obesity, Nutrition, Exercise & Eating Disorders, University of Sydney, Sydney, NSW, Australia.

出版信息

Australas Med J. 2014 Oct 31;7(10):405-15. doi: 10.4066/AMJ.2014.2181. eCollection 2014.

Abstract

The prevalence of type 2 diabetes mellitus (T2DM) is rising in Australia. Sodium glucose co-transporter 2 (SGLT2) inhibitors are an emerging treatment for T2DM. SGLT2 inhibitors offer a novel approach to lowering hyperglycaemia by suppressing renal glucose reabsorption and increasing urinary glucose excretion. The increased urinary glucose excretion has also been associated with caloric loss and osmotic diuresis. Dapagliflozin and canagliflozin are the SGLT2 inhibitors that are approved for clinical use in the US, the European Union (EU), and Australia. Their use results in reductions in HbA1c and body weight across a broad range of patient populations ranging from drug-naive patients to those who require additional therapy due to inadequate glycaemic control on their existing treatment. In addition, reductions in blood pressure (BP), particularly systolic BP, have also been noted. SGLT2 inhibitors are generally well tolerated with low rates of adverse events. Episodes of hypoglycaemia were mostly classified as minor, with low and balanced rates of severe hypoglycaemia across studies. The proportions of patients with genital infections and urinary tract infections were higher with dapagliflozin and canagliflozin versus their comparators. However, these infections were generally mild-to-moderate in intensity, treated with standard antimicrobial therapies, and rarely led to discontinuation. No dosage adjustments for dapagliflozin and canagliflozin are recommended for normal-to-mild renal impairment. Dapagliflozin and canagliflozin are not recommended for use in patients with eGFR<60 and <45mL/min/1.73m(2), respectively. Overall, SGLT2 inhibitors have shown the potential to become an important addition to the treatment armamentarium for effective management of patients with T2DM.

摘要

2型糖尿病(T2DM)在澳大利亚的患病率正在上升。钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂是一种新兴的T2DM治疗方法。SGLT2抑制剂通过抑制肾脏对葡萄糖的重吸收和增加尿糖排泄,提供了一种降低高血糖的新方法。尿糖排泄增加还与热量损失和渗透性利尿有关。达格列净和卡格列净是在美国、欧盟(EU)和澳大利亚被批准用于临床的SGLT2抑制剂。它们的使用可使从初治患者到因现有治疗血糖控制不佳而需要额外治疗的广泛患者群体的糖化血红蛋白(HbA1c)和体重降低。此外,还观察到血压(BP)降低,尤其是收缩压。SGLT2抑制剂一般耐受性良好,不良事件发生率较低。低血糖发作大多被归类为轻度,各研究中严重低血糖的发生率较低且平衡。与对照药物相比,达格列净和卡格列净治疗的患者发生生殖器感染和尿路感染的比例更高。然而,这些感染一般强度为轻至中度,采用标准抗菌疗法治疗,很少导致停药。对于正常至轻度肾功能损害患者,不建议调整达格列净和卡格列净的剂量。对于估算肾小球滤过率(eGFR)分别<60和<45mL/min/1.73m²的患者,不建议使用达格列净和卡格列净。总体而言,SGLT2抑制剂已显示出有可能成为有效管理T2DM患者治疗手段的重要补充。

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