仿制与原研维格列汀片治疗2型糖尿病有效性和安全性比较的真实世界研究

Comparison of efficacy and safety of generic versus original vildagliptin tablets in type 2 diabetes mellitus: a real world study

目的比较第三批国家集中带量采购中标药品齐鲁制药有限公司生产的维格列汀片(仿制药)与诺华制药有限公司生产的维格列汀片(原研药)治疗2型糖尿病(T2DM)的有效性和安全性。方法研究设计为多中心回顾性队列研究, 研究对象为2020年1月至2021年12月于珠海市人民医院、中山市人民医院、江门市中心医院和中国人民解放军南部战区总医院门诊应用维格列汀片治疗的T2DM患者。利用医院电子病历系统收集符合纳入标准患者的门诊病历资料并提取相关临床数据。将患者分为仿制药组和原研药组, 为排除混杂因素的干扰, 对入选患者进行倾向性评分匹配。有效性评估指标为用药1年内糖化血红蛋白(HbA1c)和空腹血糖(FPG)的下降幅度, 应用广义线性回归模型分析HbA1c和FPG下降幅度的影响因素;安全性评估指标为用药1年内不良事件发生率。结果 4家医院共收集到4 511例服用维格列汀片治疗的T2DM患者, 仿制药组3 039例, 原研药组1 472例。用药后2组患者HbA1c和FPG均较用药前下降, 仿制药组患者HbA1c和FPG下降幅度与原研药组比较差异均无统计学意义[0.50(0.05, 2.30)%比0.90(-0.10, 1.70)%, Z=0.235, P=0.814;0.59(-0.40, 2.20)mmol/L比1.00(-0.61, 2.32)mmol/L, Z=0.421, P=0.674]。广义线性回归模型分析结果显示, 治疗药物未影响HbA1c和FPG的下降幅度(P=0.627, P=0.478)。仿制药组患者用药1年内不良事件发生率和低血糖发生率与原研药组比较, 差异均无统计学意义[1.6‰(5/3 039)比2.7‰(4/1 472), P=0.721;0.7‰(2/3 039)比0.7‰(1/1 472), P=1.000]。结论齐鲁制药有限公司仿制维格列汀片治疗T2DM的有效性和安全性与原研药基本一致。

Objective To compare the efficacy and safety of vildagliptin tablets(the generic drug)manufactured by Qilu Pharmaceutical Co.,Ltd.and vildagliptin tablets(the original drug)manufactured by Novartis Pharmaceutical Co.,Ltd.in the treatment of type 2 diabetes mellitus(T2DM)in third round of national centralized volume-based procurement.Methods The study design was a multicenter retrospective cohort study.The study subjects were T2DM patients treated with vildagliptin tablets at the Outpatient Department of Zhuhai People′s Hospital,Zhongshan City People′s Hospital,Jiangmen Central Hospital,and General Hospital of Southern Theater Command of PLA from January 2020 to December 2021.Using the hospital electronic medical record system,medical records in outpatients who met the inclusion criteria were collected,and relevant clinical data were extracted.The patients were divided into generic drug group and original drug group.To exclude the interference of confounding factors,the propensity score matching method was used.The efficacy evaluation index was the magnitude of hemoglobin A1c(HbA1c)and fasting plasma glucose(FPG)reductions within one year after administration.Generalized linear regression model was used to analyze the influencing factors for the magnitude of HbA1c and FPG reduction.The safety evaluation index was the incidence of adverse events within one year of drug use.Results A total of 4511 patients with T2DM who were treated with vildagliptin tablets were collected from 4 hospitals,including 3039 in the generic drug group and 1472 in the original drug group.After treatment,the HbA1c and FPG in patients of the 2 groups decreased compared with those before treatment.The magnitude of HbA1c and FPG reductions in patients of the generic drug group were not significantly different from those in the original drug group[0.50(0.05,2.30)%vs.0.90(-0.10,1.70)%,Z=0.235,P=0.814;0.59(-0.40,2.20)mmol/L vs.1.00(-0.61,2.32)mmol/L,Z=0.421,P=0.674].The results of generalized linear regression model analysis showed that the therapeutic drugs did not affect the magnitude of HbA1c and FPG reductions(P=0.627,P=0.478).Compared with the original drug group,the incidences of adverse events and hypoglycemia in the generic drug group were not statistically significant[1.6‰(5/3039)vs.2.7‰(4/1472),P=0.721;0.7‰(2/3039)vs.0.7‰(1/1472),P=1.000].Conclusion The efficacy and safety of generic vildagliptin tablets manufactured by Qilu Pharmaceutical Co.,Ltd.were generally consistent with those of the original drug in the treatment of T2DM.