Katsiki Niki, Mikhailidis Dimitri P, Theodorakis Michael J
Second Propedeutic Department of Internal Medicine, Medical School, Aristotle; University of Thessaloniki, Hippocration Hospital, Thessaloniki, Greece.
Dept. of Clinical Biochemistry, Royal Free Hospital campus, University College London Medical School, University College London (UCL), Pond Street, London NW3 2QG, United Kingdom.
Curr Pharm Des. 2017;23(10):1522-1532. doi: 10.2174/1381612823666170113152742.
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a novel category of oral antidiabetic drugs that inhibit renal glucose reabsorption and increase renal glucose excretion, thus lowering plasma glucose levels. This unique mechanism of SGLT2i action is insulin independent, thus improving glycemic control without promoting hypoglycemia in the absence of exogenously administered insulin.
The present narrative review addresses the putative associations between SGLT2i and several cardiovascular (CV) and microvascular risk factors, as well as their effects on cardiac and renal function.
SGLT2i improve several CV risk factors, including fasting and postprandial plasma glucose levels, lipids, blood pressure, body weight, serum uric acid and arterial stiffness. These drugs may also favorably modulate cardiac and renal function via their effects on inflammation, oxidative stress, diuresis, fluid and sodium retention, myocardial function, vascular resistance and 'fuel' metabolism. In the EMPA-REG OUTCOME study, the first published large CV outcome SGLT2i trial, empagliflozin significantly reduced the primary composite outcome (i.e. CV death, nonfatal myocardial infarction or stroke) and all-cause death as well as hospitalization for heart failure. In addition, empagliflozin was associated with a slower progression of kidney disease and lower rates of clinically relevant renal events than was placebo when added to standard care in patients at high CV risk.
Multiple metabolic benefits may account for the positive clinical outcomes in the EMPA-REG OUTCOME study. Ongoing CV outcome trials involving other SGLT2i will help establish whether the reported CV and microvascular risk benefits are compound-specific or drug class effects.
钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）是一类新型口服抗糖尿病药物，可抑制肾脏对葡萄糖的重吸收，增加肾脏葡萄糖排泄，从而降低血糖水平。SGLT2i这种独特的作用机制不依赖胰岛素，因此在未使用外源性胰岛素的情况下，可改善血糖控制而不引发低血糖。
本叙述性综述探讨了SGLT2i与几种心血管（CV）和微血管危险因素之间的假定关联，以及它们对心脏和肾脏功能的影响。
SGLT2i可改善多种心血管危险因素，包括空腹和餐后血糖水平、血脂、血压、体重、血清尿酸和动脉僵硬度。这些药物还可能通过对炎症、氧化应激、利尿、液体和钠潴留、心肌功能、血管阻力和“燃料”代谢的影响，对心脏和肾脏功能产生有益调节。在EMPA-REG OUTCOME研究中，这是首个发表的大型SGLT2i心血管结局试验，恩格列净显著降低了主要复合结局（即心血管死亡、非致死性心肌梗死或中风）、全因死亡以及因心力衰竭住院的发生率。此外，在心血管高危患者中，恩格列净与标准治疗联合使用时，与安慰剂相比，可减缓肾病进展，并降低临床相关肾脏事件的发生率。
多种代谢益处可能是EMPA-REG OUTCOME研究中出现积极临床结局的原因。正在进行的涉及其他SGLT2i的心血管结局试验将有助于确定所报道的心血管和微血管风险益处是特定化合物的作用还是药物类别的效应。
