国产艾塞那肽注射液治疗2型糖尿病的疗效和安全性：一项多中心随机对照非劣效性研究

Efficacy and safety of domestic exenatide injection in treating type 2 diabetes： A muiticenter, randomized, controlled, and non-inferiority trial

目的以进口艾塞那肽注射液为阳性对照，评价国产艾塞那肽注射液治疗二甲双胍、胰岛素促泌剂单药或联合治疗血糖控制不佳的2型糖尿病患者的疗效和安全性。方法采用多中心、随机、平行对照的非劣效性研究设计，纳入240例2型糖尿病患者，按照1：1比例随机分为试验组和对照组，分别添加国产或进口艾塞那肽注射液治疗16周。主要疗效指标是HbAIC降幅，次要疗效指标包括治疗后达到HbAIC〈7．0％的受试者比率，空腹血糖（FPG）、标准餐后2h血糖（2hPG）、7点血糖自我监测（7P—SMBG）及体重的变化。结果在符合方案集受试者中，治疗16周后，试验组和对照组校正后HbAIC平均降幅分别为-1．07％和-1．06％，试验组与对照组间HbAIC平均降幅差值的最小二乘均数的双侧95％置信区间下限为-0．29％，大于预先设定的-0．35％非劣效界值，提示非劣效性假设成立。试验组和对照组治疗后达到HbAIC〈7．0％的受试者比率分别为56．19％和54．08％（P〉0．05）。2组间FPG、2hPG、7P—SMBG及体重的治疗前后变化值未见显著差异（P〉0．05）。此外，2组问低血糖事件和不良事件的发生率未见显著差异（P〉0．05）。结论在二甲双胍、胰岛素促泌剂单药或联合治疗血糖控制不佳的2型糖尿病患者中．添加国产艾塞那肽注射液的疗效不劣于进口艾塞那肽注射液，并且具有相似的安全性。

Objective To investigate the efficacy and safety of domestic exenatide injection versus imported exenatide injection in type 2 diabetic patients with inadequate glycemic control on monotherapy or combination therapy of metformin and insulin seeretagogues. Methods A multicenter, randomized, parallel-controlled, and non- inferiority trial was carried out. A total of 240 subjects were randomized at a 1 ： 1 ratio to add domestic exenatide injection （ trial group ） or imported exenatide injection （ control group ） on the background therapies The primary endpoint of efficacy was HbAm change from baseline to week 16. The secondary endpoints of efficacy were the proportion of HbAIC 〈7.0% , and the changes in fasting plasma glucose （FPG） , 2 h plasma glucose after standard meal （2hPG） , 7-point self monitoring of blood glucose （7P-SMBG） , and body weight from baseline to week 16. Results Among subjects of per-protocol sets, adjusted mean HbAIC reduction was -1.07% in the trial group versus -1.06% in the control group after 16 weeks of treatment. The lower boundary of the two-sided 95% confidence intervals of the mean HhAic reduction difference between the trial and control groups was -0.29% , which was more than -0.35%, suggesting that the predefined statistical criterion for non-inferiority was achieved. The proportions of subjects achieving HbAm〈7.0% at the end of the 16-week treatment were 56.19% and 54.08% in the trial and control groups, respectively （P〉0.05）. The changes in FPG, 2hPG, 7P-SMBG and body weight from baseline to week 16 were comparable between the two groups （all P〉0. 05 ）. Moreover, the incidences of hypoglycemia and adverse events were similar between the two groups （ both P 〉 0.05 ）. Conclusion In type 2 diabetic patients inadequately controlled by monotherapy or combination therapy of metformin and insulin secretagogues, the efficacy of cotreatment with domestic exenatide injection is not inferior to that of imported product ones, with a similar safety profile.