CORE糖尿病模型预测利拉鲁肽联合二甲双胍治疗2型糖尿病的长期健康结果

目的预测利拉鲁肽联用二甲双胍治疗2型糖尿病的长期健康结果。方法临床数据来源于国际多中心随机对照双盲临床试验NCT00614120,入组对象为来自中国、印度和韩国的2型糖尿病患者。选取利拉鲁肽1.2 mg·d~(-1)组(n=233)、利拉鲁肽1.8 mg·d~(-1)组(n=234)和格列美脲4.0 mg·d~(-1)组(n=231)的患者作为研究对象,每组患者均联用二甲双胍1.5～2.0 g·d~(-1),3组完成试验分别为187例、175例和215例。应用CORE糖尿病模型,输入16 wk临床试验前后患者机体参数改变值,模拟患者终身(30年)治疗健康结果。结果与格列美脲4.0 mg·d~(-1)组相比,利拉鲁肽1.2 mg·d~(-1)组患者背景型视网膜病变、终末期肾病、首次足溃疡和充血性心力衰竭死亡的累积发病率分别降低0.195%、0.086%、0.020%和0.528%,存活率增加了0.32%,预期寿命增加0.018年,质量调整生命年增加0.11年;利拉鲁肽1.8 mg·d~(-1)组以上4种并发症的累积发病率分别降低0.607%、0.116%、0.337%和0.626%,存活率增加了0.42%,预期寿命增加0.051年,质量调整生命年增加0.108年。敏感度分析结果显示,当模拟时间跨度分别设为10年、20年、35年,贴现率分别设置为0和5%时,与格列美脲4.0 mg·d~(-1)组的模拟结果相比,利拉鲁肽1.2 mg·d~(-1)组和1.8 mg·d~(-1)组均获得较长的存活率、预期寿命和质量调整生命年。结论与格列美脲联用二甲双胍相比,利拉鲁肽联用二甲双胍能够延缓并减少2型糖尿病患者并发症的发生,增加存活率、预期寿命与质量调整生命年。

Long term health outcomes of liraglutide combined with metformin in type 2 diabetes patients:an analysis using CORE diabetes model

AIM To evaluate the long-term health outcomes of liraglutide combined with metformin in patients with type 2 diabetes mellitus(T2DM).METHODS Simulated cohorts and treatment effects were derived from NCT00614120 clinical trial held in China,South Korea and India.The patients with T2DM in the three groups received liraglutide 1.2 mg·d~(-1)(n=233),liraglutide 1.8 mg·d~(-1)(n=234),and glimepiride 4.0 mg·d~(-1)(n=231),respectively,combined with metformin 1.5～2.0 g·d~(-1)for 16 weeks,and 187,175, 215 patients completed the trial in each group.A published and validated computer simulation model of diabetes (CORE diabetes model)was used to project long-term health outcomes(30 years).RESULTS Compared with glimepiride 4.0 mg·d~(-1)group,the cumulative incidences of background retinopathy,end stage renal disease, foot ulcer(onset),and congestive heart failure(death)event were reduced by 0.195%,0.086%,0.020%, 0.528%respectively in liraglutide 1.2 mg·d~(-1)group,and 0.607%,0.116%,0.337%,0.626%respectively in liraglutide 1.8 mg·d~(-1)group.Compared with glimepiride 4.0 mg·d~(-1)group,the survival rate was increased by 0.32%and 0.42%,the discounted life expectancy was increased by 0.018 year and 0.051 year,and quality adjusted life years(QALY)was increased by 0.11 and 0.108 in liraglutide 1.2 mg·d~(-1)and liraglutide 1.8 mg·d~(-1) group,respectively.The results of the sensitivity analysis showed that the liraglutide 1.2 mg·d~(-1)and liraglutide 1.8 mg·d~(-1)were superior to glimepiride 4.0 mg·d~(-1)in the survival rate,the discounted life expectancy and QALY when the time span was set to 10,20 and 35,and the discount rate was set to 0 and 5%.CONCLUSION Compared with glimepiride combined with metformin,liraglutide combined with metformin can delay the onset and reduce lifetime cumulative incidence of diabetes complications,and improve the survival rate,the life expectancy and QALY in patients with T2DM.