SGLT2 Inhibitors and Cardiovascular Risk: Lessons Learned From the EMPA-REG OUTCOME Study
SGLT2 Inhibitors and Cardiovascular Risk: Lessons Learned From the EMPA-REG OUTCOME Study
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DOI：
10.2337/dc16-0041
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发表时间：
2016-05-01
期刊：
影响因子：
16.2
通讯作者：
DeFronzo, Ralph A.
中科院分区：
文献类型：
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作者：
Abdul-Ghani, Muhammad;Del Prato, Stefano;DeFronzo, Ralph A.
虽然心血管（CV）死亡率是2型糖尿病（T2DM）患者死亡的主要原因，但血浆葡萄糖浓度的降低对心血管疾病（CVD）风险的影响很小。因此，需要新的策略来降低2型糖尿病患者的心血管疾病风险。最近发表的BI 10773（恩帕列净）2型糖尿病患者心血管结局事件试验（EMPA-REG Outcome）研究表明，在具有高CVD风险的2型糖尿病患者中，恩帕列净将主要不良心脏事件终点（CV死亡、非致死性心肌梗死、非致死性卒中）降低了14%。这一有益效果是由于心血管死亡率降低38%，而非致死性心肌梗死或中风没有显著降低。恩帕列净还导致心力衰竭住院率降低35%，而不影响不稳定心绞痛住院率。尽管钠-葡萄糖共转运蛋白2抑制剂具有多种代谢益处（降低HbA（1c）、体重和血压以及增加高密度脂蛋白胆固醇），所有这些都可以降低心血管疾病的风险，但CV死亡率的降低不太可能用恩格列净的代谢作用来解释。更有可能的是，血流动力学效应，特别是降低血压和减少细胞外体积，是心血管疾病死亡率和心力衰竭住院率降低的原因。从这个角度来看，我们将讨论恩格列净这些有益作用的可能机制及其对2型糖尿病患者护理的意义。
Although cardiovascular (CV) mortality is the principal cause of death in individuals with type 2 diabetes (T2DM), reduction of plasma glucose concentration has little effect on CV disease (CVD) risk. Thus, novel strategies to reduce CVD risk in T2DM patients are needed. The recently published BI 10773 (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) study demonstrated that in T2DM patients with high CVD risk empagliflozin reduced the primary major adverse cardiac event end point (CV death, nonfatal myocardial infarction, nonfatal stroke) by 14%. This beneficial effect was driven by a 38% reduction in CV mortality with no significant decrease in nonfatal myocardial infarction or stroke. Empagliflozin also caused a 35% reduction in hospitalization for heart failure without affecting hospitalization for unstable angina. Although sodium-glucose cotransporter 2 inhibitors exert multiple metabolic benefits (decreases in HbA(1c), body weight, and blood pressure and an increase in HDL cholesterol), all of which could reduce CVD risk, it is unlikely that the reduction in CV mortality can be explained by empagliflozin's metabolic effects. More likely, hemodynamic effects, specifically reduced blood pressure and decreased extracellular volume, are responsible for the reduction in CV mortality and heart failure hospitalization. In this Perspective, we will discuss possible mechanisms for these beneficial effects of empagliflozin and their implications for the care of T2DM patients.