通化东宝利拉鲁肽注射液对比诺和力^(®)治疗2型糖尿病的有效性及安全性研究:一项多中心、随机、开放、平行对照、Ⅲ期临床研究  

Efficacy and safety of Tonghua Dongbao liraglutide injection versus Victoza in the treatment of type 2 diabetes mellitus:a multicenter,randomized,open,parallel controlled,phaseⅢclinical study

作　　者：顾楠[1] 郭晓蕙[1] 逄曙光[2] 成志锋[3] 王海芳[4] 耿建林[5] 孙皎 吕述军[7] 符文燕 彭辉 李顺斌[10] 马瑜瑾[11] 周冬梅 涂萍 史晓艳 鲁一兵[15] 杨静[16] 章秋[17] 叶山东 刘精东[19] 孙春梅[20] Gu Nan;Guo Xiaohui;Pang Shuguang;Cheng Zhifeng;Wang Haifang;Geng Jianlin;Sun Jiao;Lyu Shujun;Fu Wenyan;Peng Hui;Li Shunbin;Ma Yujin;Zhou Dongmei;Tu Ping;Shi Xiaoyan;Lu Yibing;Yang Jing;Zhang Qiu;Ye Shandong;Liu Jingdong;Sun Chunmei(Department of Endocrinology,Peking University First Hospital,Beijing 100034,China;Department of Endocrinology,Jinan Central Hospital,Jinan 250000,China;Department of Endocrinology,the Fourth Affiliated Hospital of Harbin Medical University,Harbin 150006,China;Department of Endocrinology,First Hospital of Handan,Handan 056002,China;Department of Endocrinology,Hengshui People's Hospital(Harrison International Peace Hospital),Hengshui 053000,China;Department of Endocrinology,East China Hospital,Fudan University,Shanghai 200040,China;Department of Endocrinology,Huai'an First Hospital Affiliated to Nanjing Medical University,Huai'an 211103,China;Department of Endocrinology,Tonghua Central Hospital,Tonghua 134099,China;Department of Endocrinology,Yichun People's Hospital,Yichun 336000,China;Department of Endocrinology,Huzhou Central Hospital,Huzhou 313000,China;Department of Endocrinology,the First Affiliated Hospital of Henan University of Science and Technology,Luoyang 471003,China;Department of Endocrinology,Affiliated Hospital of Xuzhou Medical University,Xuzhou 221006,China;Department of Endocrinology,Nanchang Third Hospital,Nanchang 330009,China;Department of Endocrinology,Luzhong Hospital,Peking University Medical College,Zibo 255400,China;Department of Endocrinology,the Second Affiliated Hospital of Nanjing Medical University,Nanjing 210000,China;Department of Endocrinology,the First Hospital of Shanxi Medical University,Taiyuan 030032,China;Department of Endocrinology,the First Affliated Hospital of Anhui Medical University,Hefei 230022,China;Department of Endocrinology,the First Affiliated Hospital of University of Science and Technology of China,Anhui Provincial Hospital,Hefei 230001,China;Department of Endocrinology,Jiangxi Provincial People's Hospital,Nanchang 330006,China;Depar

机构地区：[1]北京大学第一医院内分泌科,北京100034 [2]济南市中心医院内分泌科,济南250000 [3]哈尔滨医科大学附属第四医院内分泌科,哈尔滨150006 [4]邯郸市第一医院内分泌科,邯郸056002 [5]衡水市人民医院(哈励逊国际和平医院)内分泌科,衡水053000 [6]复旦大学附属华东医院内分泌科,上海200040 [7]南京医科大学附属淮安第一医院内分泌科,淮安211103 [8]通化市中心医院内分泌科,通化134099 [9]宜春市人民医院内分泌科,宜春336000 [10]湖州市中心医院内分泌科,湖州313000 [11]河南科技大学第一附属医院内分泌科,洛阳471003 [12]徐州医科大学附属医院内分泌科,徐州221006 [13]南昌市第三医院内分泌科,南昌330009 [14]北大医疗鲁中医院内分泌科,淄博255400 [15]南京医科大学第二附属医院内分泌科,南京210000 [16]山西医科大学第一医院内分泌科,太原030032 [17]安徽医科大学第一附属医院内分泌科,合肥230022 [18]中国科学技术大学第一附属医院安徽省立医院内分泌科,合肥230001 [19]江西省人民医院内分泌科,南昌330006 [20]内蒙古包钢医院内分泌科,包头014010

出　　处：《中华糖尿病杂志》2024年第8期840-848,共9页CHINESE JOURNAL OF DIABETES MELLITUS

摘　　要：目的探讨通化东宝利拉鲁肽注射液(统博力)对比诺和力^(®)治疗2型糖尿病(T2DM)的有效性及安全性。方法为多中心、随机、开放、平行、阳性药物对照的Ⅲ期临床研究,等效设计。纳入2019年4月19日至2021年3月19日来自国内39家研究中心的应用二甲双胍、磺脲类药物或两者联合治疗均血糖控制不佳的T2DM患者为受试者,根据研究前口服降糖药治疗分层,按照1∶1的比例采用分层区组随机将其随机分配至统博力组和诺和力^(®)组。治疗26周后,比较两组受试者治疗前后糖化血红蛋白(HbA_(1c))、FPG、7点自测血糖的变化、低血糖事件和不良事件发生率、抗药物抗体(ADA)的发生率。有效性指标分析采用修订的意向性治疗(mITT)人群和符合方案集(PPS),安全性分析采用安全性数据集(SS)。采用配对t检验比较治疗前后相应指标的差异,采用独立样本t检验、Wilcoxon秩和检验、χ^(2)检验或Fisher精确检验进行组间比较,采用重复测量混合效应模型(MMRM)分别比较两组受试者第26周HbA_(1c)、FPG、7点自测血糖相对其基线变化的差异。采用Cochran-Mantel-Haenzel检验比较两组第26周时HbA_(1c)<7%的比例,并计算两组率差的95%CI。采用Pearsonχ2检验比较两组间治疗期间的不良事件(TEAE)、低血糖事件、ADA的发生率。结果共524例受试者随机入组,共482例受试者完成研究(统博力组243例,诺和力^(®)组239例)。所有524例受试者均被纳入mITT人群,434例受试者被纳入PPS,262例患者纳入SS。经过26周的治疗,统博力组和诺和力^(®)组受试者的HbA_(1c)分别下降1.640%±1.011%和1.620%±1.106%,两组间变化值的最小二乘均值之差(95%CI)为0(-0.18%~0.18%),差异在±0.4%的预定范围内,认为统博力与诺和力^(®)等效。两组第26周FPG分别下降(2.137±2.489)mmol/L和(2.004±2.331)mmol/L,两组间变化值的最小二乘均值之差(95%CI)为0.080(-0.280~0.439)mmol/L,差异无统计学意义Objective To explore the efficacy and safety of Tonghua Dongbao(TD)liraglutide injection(Tongboli)versus Victoza in the treatment of type 2 diabetes mellitus(T2DM).Methods This was a multicenter,randomized,open-label,parallel,positive drug controlled phaseⅢclinical study with an equivalent design.Patients with T2DM who received metformin,sulfonylureas or a combination of metformin and sulfonylureas from 39 research centres in China from April 19,2019 to March 19,2021 were included.They were randomly assigned to TD liraglutide(Tongboli)group and Victoza group according to the ratio of 1∶1.After 26 weeks of treatment,the changes of glycated hemoglobin A_(1c)(HbA_(1c)),venous fasting plasma glucose(FPG),7-point self-monitored blood glucose,incidence of hypoglycemic events and adverse events,and the incidence of anti-drug antibody(ADA)were compared between the two groups before and after treatment.The modified intention-to-treat(mITT)population and per protocol set(PPS)were used for efficacy index analysis,and the safety data set(SS)was used for safety analysis.Paired t-test was used to compare the differences in the respective before and after treatment indicatiors.Independent sample t-test,Wilcoxon rank sum test,χ^(2) test or Fisher exact test were used to compare the differences between groups.Repeated-measures mixed-effect model(MMRM)was used to compare the changes in HbA_(1c),FPG and 7-point self-monitored blood glucose from baseline at the 26th week.The Cochran-Mantel-Haenzel test was used to compare the proportions of HbA_(1c)<7%in the two groups at the 26th week,and the 95%CI of the rate difference between the two groups was calculated.Pearsonχ^(2) test was used to compare the incidence of treatment emergency adverse event(TEAE),hypoglycemic events and ADA between the two groups during treatment.Results A total of 524 subjects were randomly enrolled and 482 subjects completed the study cases in the Tongboli group(n=243)and Victoza group(n=239).All 524 subjects were included in the mITT population,434 su

关 键 词：糖尿病 2型 利拉鲁肽注射液 有效性 安全性 

分 类 号：R587.1[医药卫生—内分泌]