摘要
目的:评估真实世界中2型糖尿病(type 2 diabetes mellitus,T2DM)患者在二甲双胍治疗基础上联用西格列汀对心血管不良事件的发生风险的影响。方法:使用来自宁波市鄞州区域健康信息平台的真实世界数据,选取2017年1月1日至2022年12月31日期间,在平台中具有诊疗记录的T2DM患者。根据其用药情况,将其分二甲双胍联用西格列汀组(联用组)以及二甲双胍单用药组(单用组)。根据用药索引日期构建一系列回顾性队列,并使用倾向性评分匹配,将可能与结局有关的基线协变量纳入模型,用单用组研究对象匹配联用组研究对象,以增加组间基线特征的可比性,构建最终的回顾性队列。随访终止时间为结局发生、死亡或者是研究结束时间(2022年12月31日),以先发生者为准。观察结束后使用Cox比例风险模型估算两组间三点主要心血管不良事件(3-point major adverse cardiovascular events,3P-MACE)复合结局(心血管死亡、心肌梗死、卒中)以及各次要结局发生的风险比(hazard ratio,HR)及其95%置信区间(confidence interval,CI)。结果:倾向性评分匹配前,联用组基线使用胰岛素、α糖苷酶抑制剂、钠-葡萄糖转运体2抑制剂(sodium-glucose transporter 2 inhibitors,SGLT-2I)、格列奈类降糖药的患者比例大于单用组,且联用组基线空腹血糖(fasting blood glucose,FBG)与糖化血红蛋白(hemoglobin A1c,HbA1c)水平高于单用组。在倾向性评分匹配后,联用组和单用组各纳入5416例研究对象,组间基线特征均得到有效平衡。两组3P-MACE的发病密度分别为6.41/100人年和6.35/100人年。与单用组相比,联用组3P-MACE发生风险不增加也不降低(HR=1.00,95%CI:0.91~1.10)。次要结局比较,联用组患者心血管死亡发生率低于单用组(HR=0.59,95%CI:0.41~0.85),未发现二甲双胍联用西格列汀与心肌梗死和卒中发生风险的关联(HR=1.12,95%CI:0.89~1.41;HR=0.99,95%CI:0.91~1.12)。结论:在我国宁波市鄞州区T2DM患者中,与单用二甲双胍相比,二甲双胍联用西格列汀治疗可能降低心血管死亡的发生风险,且不增加或减少总体心血管事件发生风险,研究结果可为西格列汀的心血管安全性评价提供真实世界证据。
Objective:To assess the safety of sitagliptin added to metformin on cardiovascular adverse events in real world patients with type 2 diabetes mellitus(T2DM).Methods:Real world data from Yinzhou Regional Health Care Database were used to select T2DM patients with diagnosis and treatment records in the platform from January 1,2017 to December 31,2022.According to drug prescription records,the patients were divided into metformin plus sitagliptin group(combination group)and metformin monotherapy group(monotherapy group).A series of retrospective cohorts were constructed according to the index date.Finally,full retrospective cohorts were constructed according to propensity score model,including baseline covariates that might be related to outcomes,to match the subjects in the combination group and monotherapy group for the purpose of increasing the comparability of baseline characteristics.The participants were followed up from the index date until the first occurrence of the following events:Diagnosis of outcomes,death,or the end of the study period(December 31,2022).Cox proportional risk model was used to estimate the hazard ratio(HR)and 95%confidence interval(CI)of sitagliptin added to metformin on 3-point major adverse cardiovascular events(3P-MACE)combination outcome and secondary cardiovascular outcomes.Results:Before propensity score matching,the proportion of the patients in combination group using insulin,αglucosidase inhibitors,sodium-glucose transporter 2 inhibitors(SGLT-2I)and glienides at baseline was higher than that in monotherapy group,and the baseline fasting blood glucose(FBG)and hemoglobin A1c(HbA1c)levels in combination group were higher than those in monotherapy group.After propensity score matching,5416 subjects were included in the combination group and the monotherapy group,and baseline characteristics were effectively balanced between the groups.The incidence densities of 3P-MACE were 6.41/100 person years and 6.35/100 person years,respectively.Sitagliptin added to metformin did not increase or decrease the risk of 3P-MACE compared with the metformin monotherapy(HR=1.00,95%CI:0.91-1.10).In secondary outcomes analysis,the incidence of cardiovascular death was lower in the combination group than in the monotherapy group(HR=0.59,95%CI:0.41-0.85),and no association was found between sitagliptin and the risk of myocardial infarction and stroke(HR=1.12,95%CI:0.89-1.41;HR=0.99,95%CI:0.91-1.12).Conclusion:In T2DM patients in Yinzhou district of Ningbo,compared with metformin alone,sitagliptin added to metformin may reduce the risk of cardiovascular death,and do not increase the incidence of overall cardiovascular events.The results of this study can provide real-world evidence for post-marketing cardiovascular safety evaluation of sitagliptin.
作者
刘佐相
陈晓薇
赵厚宇
詹思延
孙凤
LIU Zuoxiang;CHEN Xiaowei;ZHAO Houyu;ZHAN Siyan;SUN Feng(Department of Epidemiology and Biostatistics,Peking University School of Public Health,Beijing 100191,China;Key Laboratory of Epidemiology of Major Diseases(Peking University),Ministry of Education,Beijing 100191,China;Clinical Epidemiology Research Center,Peking University Third Hospital,Beijing 100191,China;Hainan Institute of Real World Data,Qionghai 571437,Hainan,China)
出处
《北京大学学报（医学版）》
CAS
CSCD
北大核心
2024年第3期424-430,共7页
Journal of Peking University:Health Sciences
基金
国家自然科学基金(72074011)
中国药品监管科学行动计划第二批重点项目([2021]37-10)
海南省博鳌乐城国际医疗旅游先行区管理局真实世界研究专项计划项目(HNLC2022RWS012)。
