目的:关于依帕列净对具有广泛心血管风险的2型糖尿病患者的替代降糖药物的相对安全性和有效性的证据有限。EMPagliflozin的疗效和安全性(EMPRISE)队列研究旨在通过从电子医疗保健数据库中收集数据,在5年内定期监测empagliflozin的安全性和有效性。
方法:我们使用美国医疗保险和商业索赔数据库,从2014年至2019年鉴定了≥18岁的2型糖尿病患者,这些患者开始使用依帕列净或二肽基肽酶-4抑制剂(DPP-4i)。在使用143个基线特征进行1:1倾向评分匹配后,我们确定了4项先验定义的有效性结局:(1)心肌梗死(MI)或卒中;(2)心力衰竭(HHF)住院;(3)主要不良心血管事件(MACE);(4)心血管死亡率或HHF.安全性结果包括下肢截肢,非椎骨骨折,糖尿病酮症酸中毒(DKA),急性肾损伤(AKI),严重的低血糖,视网膜病变进展,短期肾癌和膀胱癌。我们估计每1000人年的HR和比率差异(RD),总体上按年龄分层,性别,基线动脉粥样硬化性心血管疾病(ASCVD)和心力衰竭。
结果:我们确定了115,116对匹配。与DPP-4i相比,empagliflozin与较低的MI/卒中风险相关(HR0.88[95%CI0.81,0.96];RD-2.08[95%CI(-3.26,-0.90]),HHF(HR0.50[0.44,0.56];RD-5.35[-6.22,-4.49]),MACE(HR0.73[0.62,0.86];RD-6.37[-8.98,-3.77])和心血管死亡率/HHF(HR0.57[0.47,0.69];RD-10.36[-12.63,-8.12])。老年人和ASCVD/心力衰竭患者的绝对获益更大。Empagliflozin与DKA风险增加相关(HR1.78[1.44,2.19];RD1.59[1.08,2.09]);AKI风险降低(HR0.62[0.54,0.72];RD-2.39[-3.08,-1.71]),低血糖(HR0.75[0.67,0.84];RD-2.46[-3.32,-1.60])和视网膜病变进展(HR0.78[0.63,0.96)];RD-9.49[-16.97,-2.10]);以及其他安全事件的类似风险。
结论:Empagliflozin相对于DPP-4i与MI或卒中的风险降低相关,HHF,MACE和心血管死亡率或HHF的复合。老年人和有ASCVD或心力衰竭病史的人的绝对风险降低更大。关于安全结果,empagliflozin与DKA风险增加和AKI风险降低相关,低血糖和进展为增生性视网膜病变,下肢截肢的短期风险没有差异,非椎骨骨折,肾脏和肾盂癌,和膀胱癌。
OBJECTIVE: Limited evidence exists on the comparative safety and effectiveness of empagliflozin against alternative glucose-lowering medications in individuals with type 2 diabetes with the broad spectrum of cardiovascular risk. The EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) cohort
study was designed to monitor the safety and effectiveness of empagliflozin periodically for a period of 5 years with data collection from electronic healthcare databases.
METHODS: We identified individuals ≥18 years old with type 2 diabetes who initiated empagliflozin or dipeptidyl peptidase-4 inhibitors (DPP-4i) from 2014 to 2019 using US Medicare and commercial claims databases. After 1:1 propensity score matching using 143 baseline characteristics, we identified four a priori-defined effectiveness outcomes: (1) myocardial infarction (MI) or stroke; (2) hospitalisation for heart failure (HHF); (3) major adverse cardiovascular events (MACE); and (4) cardiovascular mortality or HHF. Safety outcomes included lower-limb amputations, non-vertebral fractures, diabetic ketoacidosis (DKA), acute kidney injury (AKI), severe hypoglycaemia, retinopathy progression, and short-term kidney and bladder cancers. We estimated HRs and rate differences (RDs) per 1000 person-years, overall and stratified by age, sex, baseline atherosclerotic cardiovascular disease (ASCVD) and heart failure.
RESULTS: We identified 115,116 matched pairs. Compared with DPP-4i, empagliflozin was associated with lower risks of MI/stroke (HR 0.88 [95% CI 0.81, 0.96]; RD -2.08 [95% CI (-3.26, -0.90]), HHF (HR 0.50 [0.44, 0.56]; RD -5.35 [-6.22, -4.49]), MACE (HR 0.73 [0.62, 0.86]; RD -6.37 [-8.98, -3.77]) and cardiovascular mortality/HHF (HR 0.57 [0.47, 0.69]; RD -10.36 [-12.63, -8.12]). Absolute benefits were larger in older individuals and in those with ASCVD/heart failure. Empagliflozin was associated with an increased risk of DKA (HR 1.78 [1.44, 2.19]; RD 1.59 [1.08, 2.09]); decreased risks of AKI (HR 0.62 [0.54, 0.72]; RD -2.39 [-3.08, -1.71]), hypoglycaemia (HR 0.75 [0.67, 0.84]; RD -2.46 [-3.32, -1.60]) and retinopathy progression (HR 0.78 [0.63, 0.96)]; RD -9.49 [-16.97, -2.10]); and similar risks of other safety events.
CONCLUSIONS: Empagliflozin relative to DPP-4i was associated with risk reductions of MI or stroke, HHF, MACE and the composite of cardiovascular mortality or HHF. Absolute risk reductions were larger in older individuals and in those who had history of ASCVD or heart failure. Regarding the safety outcomes, empagliflozin was associated with an increased risk of DKA and lower risks of AKI, hypoglycaemia and progression to proliferative retinopathy, with no difference in the short-term risks of lower-extremity amputation, non-vertebral fractures, kidney and renal pelvis cancer, and bladder cancer.