Rastogi Ashu, Bhansali Anil
Department of Endocrinology, PGIMER, Chandigarh, 160012, India.
Diabetes Ther. 2017 Dec;8(6):1245-1251. doi: 10.1007/s13300-017-0320-1. Epub 2017 Oct 26.
EMPA-REG OUTCOME and CANVAS trials were designed to study the cardiovascular safety of empagliflozin and canagliflozin, respectively. Both studies were sufficiently powered to study the non-inferiority for cardiovascular (CV) outcomes in patients with type 2 diabetes mellitus (DM) and showed superiority for major adverse cardiovascular events and composite renal outcomes independent of glycemic control. Further, all patients in EMPA-REG had prior CV events (secondary prevention), compared to CANVAS that also included subjects with no prior CV events, indicating the beneficial effects of canagliflozin in primary prevention of CV events as well. Moreover, there seems to be ethnic variations in response to sodium-glucose cotransporter 2 inhibitors (SGLT2i) regarding CV benefits, as Blacks fared better with canagliflozin and Asians with empagliflozin. Increases in lower extremity amputation and fracture incidence were observed with canagliflozin in CANVAS and this needs further substantiation, though these events were not systematically captured in the EMPA-REG study.
EMPA-REG OUTCOME试验和CANVAS试验分别旨在研究恩格列净和卡格列净的心血管安全性。这两项研究都有足够的效力来研究2型糖尿病（DM）患者心血管（CV）结局的非劣效性，并显示出在主要不良心血管事件和复合肾脏结局方面具有优越性，且独立于血糖控制。此外，与同样纳入了无既往CV事件受试者的CANVAS试验相比，EMPA-REG OUTCOME试验中的所有患者均有既往CV事件（二级预防），这表明卡格列净在CV事件的一级预防中也有有益作用。此外，在CV获益方面，不同种族对钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）的反应似乎存在差异，因为黑人使用卡格列净效果更好，而亚洲人使用恩格列净效果更好。在CANVAS试验中，使用卡格列净观察到下肢截肢和骨折发生率增加，这需要进一步证实，尽管这些事件在EMPA-REG OUTCOME试验中未被系统记录。
