Efficacy and safety of Tonghua Dongbao liraglutide injection versus Victoza in the treatment of type 2 diabetes mellitus: a multicenter, randomized, open, parallel controlled, phase Ⅲ clinical study
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
Abstract
ObjectiveTo explore the efficacy and safety of Tonghua Dongbao (TD) liraglutide injection (Tongboli) versus Victoza in the treatment of type 2 diabetes mellitus (T2DM).
MethodsThis was a multicenter, randomized, open-label, parallel, positive drug controlled phase Ⅲ clinical 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 A1c (HbA1c), 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, χ2 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 HbA1c, 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 HbA1c<7% in the two groups at the 26th week, and the 95%CI of the rate difference between the two groups was calculated. Pearson χ2 test was used to compare the incidence of treatment emergency adverse event (TEAE), hypoglycemic events and ADA between the two groups during treatment.
ResultsA 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 subjects were included in PPS, and 262 patients were included in SS. After 26 weeks of treatment, the HbA1c of the two groups decreased by 1.640%±1.011% and 1.620%±1.106% in Tongboli group and Victoza, respectively. The difference in the least squares mean (95%CI) between the two groups was 0 (-0.18%-0.18%), and the difference was within the predetermined range of±0.4%. Tongboli and Victoza can be considered equivalent. At the 26th week, FPG decreased by (2.137±2.489) mmol/L and (2.004±2.331) mmol/L in the two groups, respectively. The difference in the least squares mean value (95%CI) between the two groups was 0.080 (-0.280-0.439) mmol/L, which was not statistically significant (P=0.663). There were 49.6% (130/262) and 50.8% (133/262) subjects in the two groups who achieved the target of HbA1c<7%, respectively. The difference in the rate (95%CI) between the two groups was -0.01% (-0.10%-0.07%, P=0.801). The incidence of TEAE in the two groups was 82.1% (215/262) and 79.0% (207/262), respectively, with no significant difference (χ2=0.78, P=0.377). There was no significant difference in the incidence of hypoglycemic events and ADA between the two groups (P>0.05).
ConclusionThe overall therapeutic effect of Tongboli and Victoza in controlling blood glucose is comparable, with good safety and clinical application value.
Key words:
Diabetes mellitus, type 2; Liraglutide injection; Effectiveness; Safety
Contributor Information
Gu Nan
Department of Endocrinology, Peking University First Hospital, Beijing 100034, China
Guo Xiaohui
Department of Endocrinology, Peking University First Hospital, Beijing 100034, China
Pang Shuguang
Department of Endocrinology, Jinan Central Hospital, Jinan 250000, China
Cheng Zhifeng
Department of Endocrinology, the Fourth Affiliated Hospital of Harbin Medical University, Harbin 150006, China
Wang Haifang
Department of Endocrinology, First Hospital of Handan, Handan 056002, China
Geng Jianlin
Department of Endocrinology, Hengshui People′s Hospital (Harrison International Peace Hospital), Hengshui 053000, China
Sun Jiao
Department of Endocrinology, East China Hospital, Fudan University, Shanghai 200040, China
Lyu Shujun
Department of Endocrinology, Huai′an First Hospital Affiliated to Nanjing Medical University, Huai′an 211103, China
Fu Wenyan
Department of Endocrinology, Tonghua Central Hospital, Tonghua 134099, China
Peng Hui
Department of Endocrinology, Yichun People′s Hospital, Yichun 336000, China
Li Shunbin
Department of Endocrinology, Huzhou Central Hospital, Huzhou 313000, China
Ma Yujin
Department of Endocrinology, the First Affiliated Hospital of Henan University of Science and Technology, Luoyang 471003, China
Zhou Dongmei
Department of Endocrinology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221006, China
Tu Ping
Department of Endocrinology, Nanchang Third Hospital, Nanchang 330009, China
Shi Xiaoyan
Department of Endocrinology, Luzhong Hospital, Peking University Medical College, Zibo 255400, China
Lu Yibing
Department of Endocrinology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210000, China
Yang Jing
Department of Endocrinology, the First Hospital of Shanxi Medical University, Taiyuan 030032, China
Zhang Qiu
Department of Endocrinology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China
Ye Shandong
Department of Endocrinology, the First Affiliated Hospital of University of Science and Technology of China, Anhui Provincial Hospital, Hefei 230001, China
Liu Jingdong
Department of Endocrinology, Jiangxi Provincial People′s Hospital, Nanchang 330006, China
Sun Chunmei
Department of Endocrinology, Baotou Iron and Steel Hospital, Baotou 014010, China
本刊2024年8月第8期请作如下5处修改：
（1）第840页第7行增加2位作者中文姓名，如下：
施晓红21 施秉银22
（2）第840页第19行中文作者单位增加2个，如下：
21复旦大学附属金山医院内分泌科，上海 201508；22西安交通大学第一附属医院内分泌科，西安 710061
（3）对应地，第841第18行增加2位作者的英文姓名，如下：
Shi Xiaohong21, Shi Bingyin22
（4）第841第39行英文作者单位增加2个，如下：
21Department of Endocrinology, Fudan University Affiliated Jinshan Hospital, Shanghai 201508, China; 22Department of Endocrinology, the First Affiliated Hospital of Xi'an Jiaotong University, Xian 710061, China
（5）第847页右半栏第12行作者贡献声明更正如下：
作者贡献声明 顾楠：起草文章、实施研究、采集数据、分析/解释数据；郭晓蕙：试验设计、实施研究、分析/解释数据、撰写文章、对文章内容进行审阅；逄曙光、成志锋、王海芳、耿建林、孙皎、吕述军、符文燕、彭辉、李顺斌、马瑜瑾、周冬梅、涂萍、史晓艳、鲁一兵、杨静、章秋、叶山东、刘精东、孙春梅、施晓红、施秉银：实施研究、采集数据、分析/解释数据、对文章内容进行审阅。更正的同时表示歉意！