上海交通大学学报（医学版）

上海交通大学学报（医学版） >

2021 , Vol. 41 >Issue 4: 473 - 478

DOI: https://doi.org/10.3969/j.issn.1674-8115.2021.04.009

论著·临床研究

探索二甲双胍减少系统性红斑狼疮患者感染事件的作用：一项Met-Lupus研究的事后分析

  • 耿时凯 ,
  • 张乐 ,
  • 王慧静 ,
  • 吕良敬 ,
  • 万伟国 ,
  • 孙芳芳 ,
  • 叶霜
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  • 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药剂科，上海 201112
    3.上海交通大学医学院附属仁济医院风湿科，上海 200001
    4.复旦大学附属华山医院风湿科，上海 200041
耿时凯（1993—），男，硕士生；电子信箱：shikai_geng@126.com|张 乐（1989—），女，博士生；电子信箱：joyce66dbl@hotmail.com。

收稿日期: 2020-05-28

  网络出版日期: 2021-05-14

基金资助

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);国家自然科学基金青年项目(71804109);上海市卫生和计划生育委员会科研课题青年项目(20174Y0040);上海交通大学医学院附属仁济医院南院国自然青年培育项目(2017PYQA08)

收起

Effect of metformin on infection event reduction in patients with systemic lupus erythematosus:a post-hoc analysis of a Met-Lupus Trial

  • Shi-kai GENG ,
  • Le ZHANG ,
  • Hui-jing WANG ,
  • Liang-jing Lü ,
  • Wei-guo WAN ,
  • Fang-fang SUN ,
  • Shuang YE
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  • 1.Department of Rheumatology, Renji Hospital South Campus, Shanghai Jiao Tong University School of Medicine, Shanghai 201112, China
    2.Department of Pharmacy, Renji Hospital South Campus, Shanghai Jiao Tong University School of Medicine, Shanghai 201112, China
    3.Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China
    4.Department of Rheumatology, Huashan Hospital, Fudan University Shanghai Medical College, Shanghai 200041, China

Received date: 2020-05-28

  Online published: 2021-05-14

Supported by

National Key Research and Development Program of China(2016YFC0903902);Three-year Action Plan of Shanghai Shenkang Hospital Development Center(16CR1013A);Youth Program of National Natural Science Foundation of China(71804109);Shanghai Health and Family Planning Commission Scientific Research Project for Youth(20174Y0040);National Natural Science Foundation Cultivation Project for Youth of Renji Hospital South Campus, Shanghai Jiao Tong University School of Medicine(2017PYQA08)

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摘要

目的·在一项多中心、随机、双盲、安慰剂对照临床研究（Met-Lupus）的基础上探索二甲双胍对中/低疾病活动度系统性红斑狼疮（systemic lupus erythematosus，SLE）患者的感染防护作用。方法·Met-Lupus研究的140例受试者被随机分为二甲双胍组（67例）和安慰剂组（73例），分别在常规治疗的基础上加入二甲双胍或安慰剂；二甲双胍目标剂量为1 500 mg/d，分3次口服。记录12个月随访期内SLE患者感染事件的发生情况，包括感染事件的类型、感染持续时间、感染严重程度，以及发生感染时实验室检查结果；比较发生和未发生感染事件受试者的临床特征，以及比较发生感染的患者中使用二甲双胍和使用安慰剂患者的临床特征。多元Logistic回归分析二甲双胍与感染事件发生的相关性，生存分析比较二甲双胍组和安慰剂组患者的无感染生存时间。结果·在12个月随访期末，未发生感染事件受试者的二甲双胍使用率（65.9%）显著高于发生感染事件的受试者（34.7%），差异有统计学意义（P=0.022），其他基线临床特征及治疗方案在感染和非感染患者间差异均无统计学意义。多元Logistic回归分析显示，二甲双胍的使用是减少SLE患者感染的独立保护因素（OR=0.423，P=0.033）。感染患者中，二甲双胍组的严重感染率较安慰剂组更低，但差异无统计学意义（5.9% vs 12.5%，P=0.466）。进一步分析显示，二甲双胍组受试者的感染持续时间［7.0（6.0，11.8）d］显著短于安慰剂组［10.0（7.0，21.8）d］，差异有统计学意义（P=0.034）；同时，二甲双胍组受试者C反应蛋白水平［2.5（2.4，6.4） mg/L］也呈现低于安慰剂组［4.5（2.5，8.9） mg/L］的趋势，但差异无统计学意义（P=0.075）。生存分析表明，二甲双胍受试者的无感染生存时间较安慰剂组显著延长（HR=0.527，95%CI 0.294~0.945，P=0.036）。结论·二甲双胍对轻/中度SLE患者可能具有潜在的减少感染事件的作用。

关键词： 系统性红斑狼疮; 二甲双胍; 感染; 随机对照研究

本文引用格式

耿时凯 , 张乐 , 王慧静 , 吕良敬 , 万伟国 , 孙芳芳 , 叶霜 . 探索二甲双胍减少系统性红斑狼疮患者感染事件的作用：一项Met-Lupus研究的事后分析[J]. 上海交通大学学报（医学版）, 2021 , 41(4) : 473 -478 . DOI: 10.3969/j.issn.1674-8115.2021.04.009

Abstract

Objective

·To evaluate the effect of metformin on reducing infection events in the systemic lupus erythematosus (SLE) patients with moderate/low disease activity based on a multicenter, randomized, double-blind, placebo-controlled clinical study (Met-Lupus Trial).

Methods

·The 140 participants in the Met-Lupus Trial were randomly divided into the metformin group (67 cases) and the placebo group (73 cases). The metformin tablets or placebo tablets were added to their standard therapy with target dose of 1 500 mg/d, three times per day. The infection events during the 12 months' follow-up of the patients were recorded, including the types of infection events, infection duration, infection severity, and laboratory results during infection. The clinical characteristics between the patients with or without infection as well as between the infected patients treated with metformin or placebo were compared. Multivariate Logistic regression analysis was used to analyze the correlation between metformin and infection events, and survival analysis was used to compare the infection-free survival time between the metformin group and the placebo group.

Results

·By 12 months of follow-up, the exposure rate of metformin in the patients without infection (65.9%) was significantly higher than that in the patients with infection (34.7%, P=0.022), while other clinical parameters were comparable. Multivariate Logistic regression analysis suggested that the use of metformin was an independent protective factor against infection in the SLE patients (OR=0.423, P=0.033). In the infected patients, the severe infection incidence in the metformin group was numerically lower than that in the placebo group, but there was no significant difference (5.9% vs 12.5%, P=0.466). Further analysis showed that the infection duration [7.0 (6.0, 11.8) d] of the metformin group was significantly lower than that of the placebo group [10.0 (7.0, 21.8) d] (P=0.034); meanwhile, the C-reactive protein in the metformin group [2.5 (2.4, 6.4) mg/L] was also lower than that in the placebo group [4.5 (2.5, 8.9) mg/L] without significant difference (P=0.075). Survival analysis showed that infection-free survival of the metformin group was significantly longer than that of the placebo group (HR=0.527, 95%CI 0.294?0.945, P=0.036).

Conclusion

·Metformin may have a potential effect on infection event reduction in the SLE patients with moderate/low disease activity.

Key words： systemic lupus erythematosus (SLE); metformin; infection; randomized controlled study

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