门冬胰岛素50注射液治疗2型糖尿病的有效性和安全性的多中心、随机、开放、平行对照Ⅲ期临床研究  

Efficacy and safety of insulin aspart 50 injection in the treatment of type 2 diabetes mellitus:a multicenter,randomized,open,parallel and phaseⅢclinical study

作　　者：帅瑛[1] 姚勇利[2] 杨涛[3] 孙皎 刘精东[5] 施秉银[6] 章秋[7] 施晓红 史晓艳 涂萍 赵冬[11] 逄曙光[12] 刘婕[13] 肖新华[14] 叶山东[15] 杨金奎[16] 周冬梅 杨文英[1] Shuai Ying;Yao Yongli;Yang Tao;Sun Jiao;Liu Jingdong;Shi Bingyin;Zhang Qiu;Shi Xiaohong;Shi Xiaoyan;Tu Ping;Zhao Dong;Pang Shuguang;Liu Jie;Xiao Xinhua;Ye Shandong;Yang Jinkui;Zhou Dongmei;Yang Wenying(Department of Endocrinology,China-Japan Friendship Hospital,Beijing 100029,China;Department of Endocrinology,Qinghai Provincial People′s Hospital,Xining 810007,China;Department of Endocrinology,Jiangsu Provincial People′s Hospital,Nanjing 210029,China;Department of Endocrinology,Huadong Hospital Affiliated to Fudan University,Shanghai 200040,China;Department of Endocrinology,Jiangxi Provincial People′s Hospital,Nanchang 330006,China;Department of Endocrinology,the First Affiliated Hospital of Xi′an Jiaotong University,Xi′an 710061,China;Department of Endocrinology,the First Affiliated Hospital of Anhui Medical University,Hefei 230022,China;Department of Endocrinology,Jinshan Hospital of Fudan University,Shanghai 201508,China;Department of Endocrinology,PKU Care Luzhong Hospital,Zibo 255411,China;Department of Endocrinology,the Third Hospital of Nanchang,Nanchang 330008,China;Department of Endocrinology,Beijing Luhe Hospital,Capital Medical University,Beijing 101199,China;Department of Endocrinology,Jinan Central Hospital,Jinan 250013,China;Department of Endocrinology,the First Affiliated Hospital of Henan University of Science and Technology,Luoyang 450052,China;Department of Endocrinology,Peking Union Medical College Hospital,Beijing 100005,China;Department of Endocrinology,Anhui Provincial Hospital,Hefei 230002,China;Department of Endocrinology,Beijing Tongren Hospital,Capital Medical University,Beijing 100005,China;Department of Endocrinology,the Affiliated Hospital of Xuzhou Medical University,Xuzhou 221004,China)

机构地区：[1]中日友好医院内分泌科,北京100029 [2]青海省人民医院内分泌科,西宁810007 [3]江苏省人民医院内分泌科,南京210029 [4]复旦大学附属华东医院内分泌科,上海200040 [5]江西省人民医院内分泌科,南昌330006 [6]西安交通大学第一附属医院内分泌科,西安710061 [7]安徽医科大学第一附属医院内分泌科,合肥230022 [8]复旦大学附属金山医院内分泌科,上海201508 [9]北大医疗鲁中医院内分泌科,淄博255411 [10]南昌市第三医院内分泌科,南昌330008 [11]首都医科大学附属北京潞河医院内分泌科,北京101199 [12]济南市中心医院内分泌科,济南250013 [13]河南科技大学第一附属医院内分泌科,洛阳450052 [14]北京协和医院内分泌科,北京100005 [15]安徽省立医院内分泌科,合肥230002 [16]首都医科大学附属北京同仁医院内分泌科,北京100005 [17]徐州医科大学附属医院内分泌科,徐州221004

出　　处：《中华糖尿病杂志》2023年第2期128-134,共7页CHINESE JOURNAL OF DIABETES MELLITUS

摘　　要：目的探讨门冬胰岛素50注射液(锐舒霖®50)治疗2型糖尿病(T2DM)的有效性及安全性。方法本研究为一项多中心、随机、开放、平行、阳性对照的Ⅲ期临床研究。自2016年7月29日至2019年9月12日纳入来自全国27家中心口服药治疗后血糖控制不佳的T2DM患者542例,根据区组随机方法将受试者以2∶1的比例分配进入锐舒霖®50组或诺和锐®50组。治疗24周后,比较两组受试者治疗前后糖化血红蛋白(HbA1c)、空腹血糖(FPG)、餐后2 h血糖(2hPG)的变化,以及试验结束时低血糖事件和不良事件发生率、门冬胰岛素特异性抗体阳性率。有效性指标采用全分析集(FAS)和符合方案集(PPS)数据分析,安全性指标采用安全性数据集(SS)分析。组内比较采用配对样本t检验,组间比较采用独立样本t检验和χ^(2)检验。结果本研究共纳入T2DM患者542例,锐舒霖®50组364例、诺和锐?50组178例。FAS受试者532例(锐舒霖®50组356例、诺和锐?50组176例),PPS受试者485例(锐舒霖®50组325例、诺和锐?50组160例),SS受试者533例(锐舒霖®50组357例、诺和锐?50组176例)。经过24周治疗后,锐舒霖®50组和诺和锐?50组T2DM患者的HbA1c分别下降1.56%±1.42%和1.54%±1.27%,FPG分别下降(1.94±3.08)和(1.43±2.53)mmol/L,2hPG分别下降(4.66±5.40)和(4.21±5.36)mmol/L,上述指标组内降幅差异均具有统计学意义(P<0.001),两组间比较差异均无统计学意义(P>0.05)。锐舒霖®50组和诺和锐?50组T2DM患者的总体低血糖事件发生率[分别为65.27%(233/357)和68.18%(120/176)]、不良事件发生率[分别为79.55%(284/357)和72.73%(128/176)]与门冬胰岛素特异性抗体阳性率[24周时分别为55.03%(186/338)和57.83%(96/166)]相近,差异均无统计学意义(P>0.05)。结论锐舒霖®50和诺和锐®50控制血糖的总体疗效和安全性相当,具有临床应用价值。Objective To explore the efficacy and safety of biphasic insulin aspart 50(Ruisulin®50)in treatment of patients with type 2 diabetes mellitus(T2DM).Methods A multicenter,randomized,open-labeled,parallel-controlled and positive control and the phaseⅢof clinical trial included the 542 T2DM patients having poor glucose control after using oral hypoglycemic drugs from July 29,2016 to September 12,2019.All patients were assigned to Ruisulin®50 group or NovoMix®50 group for 24 weeks by a ratio of 2∶1 based on block randomization.The decreased value and qualification rates of glycated hemoglobin A1c(HbA1c),fasting plasma glucose(FPG),2 h postprandial blood glucose(2hPG),the incidence of hypoglycemic and adverse events,and the positive rate of aspartic islet specific antibody were compared at the end of 24 weeks.The full analysis set(FAS)and per-protocol dataset(PPS)were used for the effectiveness index analysis,and the safety set(SS)was used for the security index analysis.Analyses of matched samples t-test,t-test,and chi-square test were used.Results All of 542 cases were included in the trial(364 cases received Ruisulin®50 therapy and 178 cases received NovoMix®50 therapy).There were 532 cases in FAS(356 cases received Ruisulin®50 therapy and 176 cases received NovoMix®50 therapy),485 cases in PPS(325 cases received Ruisulin®50 therapy and 160 cases received NovoMix®50 therapy),and 533 cases in SS(357 cases received Ruisulin®50 therapy and 176 cases received NovoMix®50 therapy).At the end of 24-week treatment period,HbA1c in Ruisulin®50 group and NovoMix®50 group decreased by 1.56%±1.42%and 1.54%±1.27%,respectively.FPG decreased by(1.94±3.08)and(1.43±2.53)mmol/L,and 2hPG decreased by(4.66±5.40)and(4.21±5.36)mmol/L,respectively.The decrease of the above indexes within the group was statistically significant(P<0.001),and there was no statistically significant difference between the two groups(P>0.05).Moreover,the incidence of hypoglycemic events was 65.27%(233/357)and 68.18%(120/176),the incidence

关 键 词：糖尿病 2型 门冬胰岛素50 有效性 安全性 

分 类 号：R587.1[医药卫生—内分泌]