二甲双胍治疗系统性红斑狼疮的临床试验后随访研究  

A long-term follow-up study after the open-label proof-of-concept trial of metformin in systemic lupus erythematosus

作　　者：刘喆[1] 王海婷[1] 王慧静 滕香宇[2] 叶霜[1] LIU Zhe;WANG Hai-ting;WANG Hui-jing;TENG Xiang-yu;YE Shuang(Department of Rheumatology,South Campus of Renji Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 201112,China;Department of Endocrinology,South Campus of Renji Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 201112,China)

机构地区：[1]上海交通大学医学院附属仁济医院南院风湿科,上海201112 [2]上海交通大学医学院附属仁济医院南院内分泌科,上海201112

出　　处：《上海交通大学学报（医学版）》2018年第10期1186-1190,共5页Journal of Shanghai Jiao tong University:Medical Science

基　　金：国家重点研发计划(2016YFC0903902);上海申康医院发展中心三年行动计划(16CR1013A)~~

摘　　要：目的·评价长期二甲双胍加载治疗对维持系统性红斑狼疮(systemic lupus erythematosus,SLE)疾病活动低风险的作用和患者长期服用二甲双胍的安全性,以及二甲双胍对SLE免疫紊乱代谢调节可能的代谢记忆效应。方法·在前期二甲双胍治疗SLE的开放对照proof-of-concept临床研究基础上,对愿意继续配合随访的受试者进行临床试验后的真实世界长期随访研究。记录并分析二甲双胍组和对照组受试者的SLE疾病活动情况与不良事件发生情况,分析二甲双胍组受试者停用二甲双胍后是否仍能维持疾病活动低风险。结果·共纳入二甲双胍组受试者29例,对照组受试者28例;二甲双胍组受试者均未出现二甲双胍相关不良反应。对照组受试者的疾病活动风险呈现出高于持续使用二甲双胍组和研究过程中停用二甲双胍组的趋势,但差异无统计学意义(P=0.326);研究初停用二甲双胍组在停用二甲双胍后,疾病活动风险逐渐与对照组趋同(P=0.998);平均使用二甲双胍2.56年的研究过程中停用二甲双胍组与平均使用二甲双胍5.00年的持续使用二甲双胍组的疾病活动风险比较,差异无统计学意义(P=0.802)。结论·长期二甲双胍加载治疗能够维持SLE疾病活动低风险并具有良好的安全性,二甲双胍对SLE免疫紊乱的代谢调节可能存在用药时间依赖的代谢记忆效应。Objective·To evaluate the efficacy and safety of a long-term adding metformin to a basic treatment strategy in systemic lupus erythematosus(SLE),and analyze whether the beneficial effects of metformin add-on treatment during the open-label proof-of-concept trial persisted during a posttrial follow-up(the metabolic memory effect),as there is a paucity of systematically collected data concerning long-term metformin use in SLE.Methods·Subjects who had participated in the open-label proof-of-concept trial and gave informed consent to this study were enrolled,and the disease flares and long-term adverse effects between metformin group and control group were compared.In addition,whether the benefit regarding decreased disease flare persisted after metformin withdrawal during the post-trial follow-up was investigated.Results·Twenty-nine subjects in the former metformin add-on strategy group and 28 subjects in the former control group were enrolled.No adverse reactions of metformin occurred during the study.The risk of disease flare in the control group was higher than that in the continuous metformin group,but the difference was not statistically significant(P=0.326).After metformin withdrawal,the risk of disease flare in the metformin group gradually increased to the control group(P=0.998).There was no significant difference between the two continuous metformin use groups whose metformin using duration are 2.56 years and 5.00 years respectively(P=0.802).Conclusion·A long-term metformin add-on treatment is security,and can keep SLE patients in a lower risk of disease flare.The metabolic regulation of metformin in SLE immune disorder may present a time-dependent metabolic memory effect.

关 键 词：系统性红斑狼疮 二甲双胍 代谢免疫 临床试验后随访 代谢记忆效应 

分 类 号：R593.241[医药卫生—内科学]