Tanaka Atsushi, Node Koichi
Department of Cardiovascular Medicine, Saga University, Saga, Japan.
Department of Cardiovascular Medicine, Saga University, Saga, Japan.
J Cardiol. 2017 Mar;69(3):501-507. doi: 10.1016/j.jjcc.2016.10.019. Epub 2016 Dec 30.
The ultimate goal of treatment in people with diabetes mellitus is to prevent development of cardiovascular (CV) disease, resulting in prolongation of healthy life expectancy. Although impaired glycemic metabolism has a central role in its pathology, a number of studies have demonstrated that remedy for its imbalance cannot necessarily be accomplished as a therapeutic goal. A comprehensive medical approach against multi-factorial pathologies in diabetes, such as insulin resistance, obesity, hypertension, and dyslipidemia, in addition to diet and exercise therapy should be rather performed in the routine clinical setting. Along with such conceptual transition, what is required in anti-diabetes agents has also changed, and several anti-diabetes agents have been newly placed on the market in this decade. Such agents are required to undergo global pre- or post-marketing clinical trials assessing CV safety. A growing body of clinical evidence from those trials is now accumulating, and empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has first demonstrated significant risk reduction, relative to placebo, in CV death, overall mortality, and hospitalization for worsened heart failure in high-risk patients with diabetes mellitus. An SGLT2 inhibitor is a unique glucose-lowering agent and at the same time has multifaceted effects on hemodynamic and metabolic parameters beyond glycemic control. A major mode of action of SGLT2 inhibitors appears to be 'glycosuria' and 'natriuresis,' leading to amelioration of systemic glycemic homeostasis and potential cardio-renal protection. However, the precise mechanisms by which SGLT2 inhibitors affect benefits on the CV systems are yet to be fully elucidated. Thus, although we are now facing several unanswered concerns lurking behind the successful trial, SGLT2 inhibitors surely play several important roles in high-quality management of not only diabetes, but also CV medicine. This review summarizes our current understandings and future perspectives of SGLT2 inhibitors in CV medicine.
糖尿病患者治疗的最终目标是预防心血管（CV）疾病的发生，从而延长健康预期寿命。尽管血糖代谢受损在其病理过程中起核心作用，但多项研究表明，纠正其失衡并不一定能作为治疗目标实现。除饮食和运动疗法外，针对糖尿病多因素病理状况（如胰岛素抵抗、肥胖、高血压和血脂异常）的综合医学方法应在常规临床环境中实施。随着这种观念的转变，抗糖尿病药物的需求也发生了变化，在这十年中有几种新型抗糖尿病药物上市。此类药物需要进行评估CV安全性的全球上市前或上市后临床试验。来自这些试验的临床证据越来越多，钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂恩格列净首次证明，相对于安慰剂，在糖尿病高危患者中可显著降低CV死亡、全因死亡率以及因心力衰竭恶化住院的风险。SGLT2抑制剂是一种独特的降糖药物，同时对血糖控制以外的血流动力学和代谢参数具有多方面影响。SGLT2抑制剂的主要作用方式似乎是“糖尿”和“利钠”，从而改善全身血糖稳态并具有潜在的心肾保护作用。然而，SGLT2抑制剂影响CV系统获益的确切机制尚未完全阐明。因此，尽管我们目前面临着成功试验背后潜藏的几个未解决问题，但SGLT2抑制剂无疑在糖尿病以及CV医学的高质量管理中发挥着重要作用。本综述总结了我们目前对SGLT2抑制剂在CV医学方面的理解以及未来展望。
