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 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 PDF全文下载地址:
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