艾塞那肽在不同基线肾功能糖尿病肾脏病患者中的肾脏有效性

Renal efficacy of exenatide in diabetic kidney disease patients with different baseline renal function

目的:评估艾塞那肽在不同基线肾功能的糖尿病肾脏病(DKD)患者中的肾脏有效性。方法:本研究为一项多中心、开放、随机、平行对照试验的亚组分析临床研究。收集2016年3月至2019年4月从4家综合性三级甲等医院(分别为南方医科大学南方医院、广东省第二中医院、广东省人民医院二沙岛分院及广东省第二人民医院)筛选估算的肾小球滤过率(eGFR)≥30 ml·min^(-1)·(1.73 m^(2))^(-1)且24 h尿白蛋白排泄率(UAER)>0.3 g/24 h的2型糖尿病(T2DM)患者。入选患者按照1∶1的比例采用随机数字表法分配至干预组或对照组并随访24周。干预组治疗方案为艾塞那肽联合甘精胰岛素;对照组治疗方案为赖脯胰岛素联合甘精胰岛素。根据基线时eGFR分期,分为G1期,eGFR≥90 ml·min^(-1)·(1.73 m^(2))^(-1);G2期,eGFR为60~89 ml·min^(-1)·(1.73 m^(2))^(-1);G3a期,eGFR为45~59 ml·min^(-1)·(1.73 m^(2))^(-1);G3b期,eGFR为30~44 ml·min^(-1)·(1.73 m^(2))^(-1)。使用重复测量的混合效应模型对全分析集中UAER的变化率按上述分组进行亚组分析。结果:92例T2DM患者被随机分配至干预组(46例)及对照组(46例)并至少使用过1次研究用药,最终81例患者(干预组43例,对照组38例)被纳入全集分析集中。全分析集中,基线时17例患者(干预组9例,对照组8例)为G1期,34例患者(干预组20例,对照组14例)为G2期,15例患者(干预组7例,对照组8例)为G3a期,15例患者(干预组7例,对照组8例)为G3b期。经过24周的干预,干预组和对照组比较,UAER在G1期亚组中减少了2.2%,差异无统计学意义(P=0.845);在G2期亚组中减少了55.9%,差异有统计学意义(P=0.015);在G3a期亚组中增加了5.4%,在G3b期亚组中减少了21.2%,差异均无统计学意义(P值分别为0.861和0.459)。结论:基线时G2期的DKD患者中应用艾塞那肽肾脏获益更大。

Objective To evaluate the renal efficacy of exenatide in diabetic kidney disease(DKD)patients with different baseline renal function.Methods Between March 2016 and April 2019,a randomized,parallel study conducted in 4 general hospitals was performed.Type 2 diabetes mellitus(T2DM)patients with an estimated glomerular filtration rate(eGFR)≥30 ml·min^(-1)·(1.73 m^(2))^(-1) and macroalbuminuria,defined as urinary albumin-creatinine ratio(UAER)>0.3 g/24 h.In this study,a computer-generated random number table was used for block randomization.The selected patients were randomized 1∶1 to receive exenatide plus glargine or lispro insulin plus glargine for 24 weeks.We investigated percentage change in UAER after 24 weeks of intervention comparing to baseline measurement according to eGFR stage at baseline[G1 stage[eGFR≥90 ml·min^(-1)·(1.73 m^(2))^(-1)];G2 stage[eGFR 60-89 ml·min^(-1)·(1.73 m^(2))^(-1)];G3a stage[eGFR 45-59 ml·min^(-1)·(1.73 m^(2))^(-1)]and G3b stage[eGFR 30-44 ml·min^(-1)·(1.73 m^(2))^(-1)].The mixed effect model of repeated measurement was used to analyze the change rate of UAER in the whole analysis set according to the above groups.Results Ninety-two patients were randomly assigned to the intervention group(n=46)and the control group(n=46),and the patients had used at least 1 study drug.Eighty-one(88.0%)patients(43 in intervention group,38 in control group)were included for the full set analysis.Seventeen patients were in G1 stage,34 in G2 stage,15 in G3a stage and 15 in G3b stage.After 24 weeks,the mean difference of the percentage change in UAER from baseline between exenatide plus insulin glargine and insulin glargine plus lispro was-55.9%(P=0.015)in patients in G2 stage at baseline.While no difference showed in the other subgroups(P>0.05).Conclusion For the DKD patients in G2 stage at baseline,the renal benefit was greater after the administration of exenatide.