SGLT-2 inhibitors and cardiovascular risk: proposed pathways and review of ongoing outcome trials.
SGLT-2 inhibitors and cardiovascular risk: proposed pathways and review of ongoing outcome trials.
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DOI：
10.1177/1479164114559852
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发表时间：
2015-03
影响因子：
2.4
通讯作者：
Johansen OE
中科院分区：
文献类型：
--
作者：
Inzucchi SE;Zinman B;Wanner C;Ferrari R;Fitchett D;Hantel S;Espadero RM;Woerle HJ;Broedl UC;Johansen OE
考虑到2型糖尿病（T2 DM）动脉粥样硬化的多方面发病机制，缓解这种风险的干预措施可能必须解决葡萄糖本身以外的心血管（CV）风险因素。钠葡萄糖协同转运蛋白-2（SGLT-2）抑制剂是一种新型的具有明显多重作用的抗高血压药物。这些药物的固有作用模式是通过增加尿糖排泄来减少肾脏对葡萄糖的重吸收，因此可独立于胰岛素分泌改善血糖控制，低血糖风险较低。在这篇综述中，我们概述了这类似乎影响的CV风险因素，并提供了6项正在进行的结局试验的设计特征和试验特征，这些试验涉及41，000多名T2 DM患者。SGLT-2抑制剂可能积极调节的葡萄糖以外的风险因素包括血压、体重、内脏肥胖、高胰岛素血症、动脉硬化、白蛋白尿、循环尿酸水平和氧化应激。另一方面，低密度脂蛋白（LDL）-胆固醇水平的小幅增加也被观察到，这在理论上可能会抵消其中的一些好处。这些效应的潜在转化影响正在通过结局试验进行测试，也在本文中进行了综述，旨在评估T2 DM的大血管和某些微血管结局。预计这些报告将于2015年晚些时候开始提交。
Given the multi-faceted pathogenesis of atherosclerosis in type 2 diabetes mellitus (T2DM), it is likely that interventions to mitigate this risk must address cardiovascular (CV) risk factors beyond glucose itself. Sodium glucose cotransporter-2 (SGLT-2) inhibitors are newer antihyperglycaemic agents with apparent multiple effects. Inherent in their mode of action to decrease glucose reabsorption by the kidneys by increasing urinary glucose excretion, these agents improve glycaemic control independent of insulin secretion with a low risk of hypoglycaemia. In this review, we outline those CV risk factors that this class appears to influence and provide the design features and trial characteristics of six ongoing outcome trials involving more than 41,000 individuals with T2DM. Those risk factors beyond glucose that can potentially be modulated positively with SGLT-2 inhibitors include blood pressure, weight, visceral adiposity, hyperinsulinaemia, arterial stiffness, albuminuria, circulating uric acid levels and oxidative stress. On the other hand, small increases in low-density lipoprotein (LDL)-cholesterol levels have also been observed for the class, which theoretically might offset some of these benefits. The potential translational impact of these effects is being tested with outcome trials, also reviewed in this article, powered to assess both macrovascular as well as certain microvascular outcomes in T2DM. These are expected to begin to report in late 2015.