甘精胰岛素注射液(HS004)和来得时^(■)治疗糖尿病的有效性和安全性比较:多中心、随机、开放、阳性药平行对照的Ⅲ期临床研究

Efficacy and safety of insulin glargine injection(HS004)compared with Lantus^(■) in diabetes:a phaseⅢmulticenter,randomized,open-label,parallel,active-controlled clinical trial

目的 比较甘精胰岛素注射液(HS004)和来得时^(■)治疗糖尿病的有效性和安全性。方法 本研究为多中心、随机、开放、平行组、阳性药平行对照的Ⅲ期临床研究,研究共筛选2017年10月至2019年9月35家中心的914例受试者,最终610例随机分配于HS004组和来得时组,治疗24周。比较两组治疗前后糖化血红蛋白(HbA1c)、空腹血糖(FPG)、餐后2 h静脉血糖(2hPG)、体重、胰岛素每日用量、胰岛素u/kg用量、不良事件的发生率和甘精胰岛素特异性抗体阳性率。结果 治疗24周后,全部人群HS004组与来得时组的HbA1c的降幅(0.84%vs 0.96%)、2型糖尿病(T2DM)受试者中两组的降幅(0.92%vs 1.02%)以及治疗12周时T2DM受试者两组HbA1c的降幅(0.92%vs 1.05%)差异均无统计学意义(P>0.05)。T2DM受试者治疗24周后,HS004组与来得时组HbA1c≤6.5%的受试者的比例分别为12.82%和8.20%,HbA1c<7.0%的受试者的比例分别为27.47%和26.17%;两组FPG较基线的平均降幅分别为1.709 mmol/L、1.950 mmol/L,2hPG的平均降幅分别为2.908 mmol/L、3.005mmol/L;两组体重较基线变化的均值分别为0.79 kg和0.97 kg;两组胰岛素每日用量均值分别为13.95 u、13.02 u;两组胰岛素u/kg用量均值分别为0.20 u/kg、0.19 u/kg,上述指标两组间差异均无统计学意义(P>0.05)。对于其中的T2DM受试者,与来得时组相比,HS004组中低血糖事件的发生率降低了0.7%,组间差异无统计学意义(P>0.05);T2DM受试者,HS004组和来得时组基线抗药物抗体(ADA)阳性率差异无统计学意义(5.80%vs 9.30%,P>0.05);治疗期间末次访视,两组ADA阳性率差异无统计学意义(12.59%vs 14.34%,P>0.05)。结论 甘精胰岛素注射液(HS004)治疗糖尿病的有效性和安全性与来得时^(■)相当,并具有良好的耐受性。

Objective To compare the efficacy and safety of insulin glargine injection(HS004)and Lantus^(■) in treating patients with diabetes mellitus.Methods This was a phaseⅢ,multicenter,randomized,open-label,parallel-group,active-controlled clinical trial.A total of 914 participants with diabetes from 35 hospitals,610 subjects of them were randomly assigned to HS004 group and Lantus^(■) group for 24 weeks.The efficacy measures included changes in glycosylated hemoglobin(HbA1c),fasting plasma glucose(FPG),2 h postprandial plasma glucose(2hPG),body weight from baseline,daily dosage of insulin,dosage of insulin u/kg.The safety outcomes included rates of hypoglycemia,adverse events and anti-insulin glargine antibody.Results After 24 weeks of treatment,there was no significant differences in the change of HbA1c of total subjects in HS004 group and Lantus^(■) group(0.84%vs 0.96%,P>0.05),so were the change of HbA1c of T2DM subjects at 24 weeks(0.92%vs 1.02%,P>0.05)and 12 weeks(0.92%vs 1.05%,P>0.05).After 24 weeks of treatment in T2DM subjects,the proportions of HbA1c≤6.5%were 12.82%in HS004 group and 8.20%in Lantus^(■) group,and the proportions of HbA1c<7.0%were 27.47%and 26.17%,respectively.FPG decreased by 1.709 mmol/L and 1.950 mmol/L from baseline in the two groups,respectively,and 2 hPG decreased by 2.908 mmol/L and 3.005 mmol/L,respectively.The mean body weight changes from baseline in the two groups were 0.79 kg and 0.97 kg,respectively.The daily dosage of insulin in the two groups was 13.95 u and 13.02 u,respectively.The dosages of insulin u/kg were 0.20 u/kg in HS004 group and 0.19 u/kg in Lantus^(■) group,respectively.In T2DM subjects,the incidence of hypoglycemia reduced by 0.7%in HS004 group compared with Lantus^(■) group,but there was no significant difference between them(P>0.05).In T2DM subjects,there was no significant difference in anti-drug antibody(ADA)positive rate at baseline(5.80%vs 9.30%,P>0.05)between the two groups,and no significant difference in the ADA positive rate at the last visit during treatment(12.59%vs 14.34%,P>0.05).Conclusion Insulin glargine injection(HS004)shows similar efficacy and safety profiles compared with Lantus^(■) in treating patients with diabetes mellitus,and insulin glargine injection(HS004)treatment was well tolerated in patients.