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

doi:10.3969/j.issn.1674-8115.2021.04.009

上海交通大学学报(医学版) ›› 2021, Vol. 41 ›› Issue (4): 473-478.doi: 10.3969/j.issn.1674-8115.2021.04.009

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¹(), 张乐²^,³(), 王慧静¹, 吕良敬³, 万伟国⁴, 孙芳芳¹(), 叶霜¹()

^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

收稿日期:2020-05-28 出版日期:2021-04-28 发布日期:2021-05-14
通讯作者: 孙芳芳,叶霜 E-mail:shikai_geng@126.com;joyce66dbl@hotmail.com;fiona_rj@163.com;ye_shuang2000@163.com
作者简介: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。
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)

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

Shi-kai GENG¹(), Le ZHANG²^,³(), Hui-jing WANG¹, Liang-jing LÜ³, Wei-guo WAN⁴, Fang-fang SUN¹(), Shuang YE¹()

^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:2020-05-28 Online:2021-04-28 Published:2021-05-14
Contact: Fang-fang SUN,Shuang YE E-mail:shikai_geng@126.com;joyce66dbl@hotmail.com;fiona_rj@163.com;ye_shuang2000@163.com
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)

摘要/Abstract

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

中图分类号:

R593.24

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.

Shi-kai GENG, Le ZHANG, Hui-jing WANG, Liang-jing LÜ, Wei-guo WAN, Fang-fang SUN, Shuang YE. Effect of metformin on infection event reduction in patients with systemic lupus erythematosus:a post-hoc analysis of a Met-Lupus Trial[J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(4): 473-478.

图/表 4

参考文献 33

1	Tsokos GC. Systemic lupus erythematosus[J]. N Engl J Med, 2011, 365(22): 2110-2121.
2	Zucchi D, Elefante E, Calabresi E, et al. One year in review 2019: systemic lupus erythematosus[J]. Clin Exp Rheumatol, 2019, 37(5): 715-722.
3	刘喆, 叶霜. 代谢与免疫: 解析系统性红斑狼疮的新视角[J]. 中华风湿病学杂志, 2016, 20(8): 505-507.
4	Hahn BH. Belimumab for systemic lupus erythematosus[J]. N Engl J Med, 2013, 368(16): 1528-1535.
5	Lai ZW, Kelly R, Winans T, et al. Sirolimus in patients with clinically active systemic lupus erythematosus resistant to, or intolerant of, conventional medications: a single-arm, open-label, phase 1/2 trial[J]. Lancet, 2018, 391(10126): 1186-1196.
6	Schneider M. Target therapy in SLE[J]. Autoimmun Rev, 2019, 18(1): 21-24.
7	Barber C, Gold WL, Fortin PR. Infections in the lupus patient: perspectives on prevention[J]. Curr Opin Rheumatol, 2011, 23(4): 358-365.
8	Danza A, Ruiz-Irastorza G. Infection risk in systemic lupus erythematosus patients: susceptibility factors and preventive strategies[J]. Lupus, 2013, 22(12): 1286-1294.
9	Morel L. Immunometabolism in systemic lupus erythematosus[J]. Nat Rev Rheumatol, 2017, 13(5): 280-290.
10	Sharabi A, Tsokos GC. T cell metabolism: new insights in systemic lupus erythematosus pathogenesis and therapy[J]. Nat Rev Rheumatol, 2020, 16(2): 100-112.
11	Teng X, Brown J, Choi SC, et al. Metabolic determinants of lupus pathogenesis[J]. Immunol Rev, 2020, 295(1): 167-186.
12	Teng X, Cornaby C, Li W, et al. Metabolic regulation of pathogenic autoimmunity: therapeutic targeting[J]. Curr Opin Immunol, 2019, 61: 10-16.
13	Yin Y, Choi SC, Xu Z, et al. Normalization of CD4⁺ T cell metabolism reverses lupus[J]. Sci Transl Med, 2015, 7(274): 274ra18.
14	Chen FC, Kung CT, Cheng HH, et al. Metformin affects serum lactate levels in predicting mortality of patients with sepsis and bacteremia[J]. J Clin Med, 2019, 8(3):318.
15	Pernicova I, Kelly S, Ajodha S, et al. Metformin to reduce metabolic complications and inflammation in patients on systemic glucocorticoid therapy: a randomised, double-blind, placebo-controlled, proof-of-concept, phase 2 trial[J]. Lancet Diabetes Endocrinol, 2020, 8(4): 278-291.
16	Wang H, Li T, Chen S, et al. Neutrophil extracellular trap mitochondrial DNA and its autoantibody in systemic lupus erythematosus and a proof-of-concept trial of metformin[J]. Arthritis Rheumatol, 2015, 67(12): 3190-3200.
17	Singhal A, Jie L, Kumar P, et al. Metformin as adjunct antituberculosis therapy[J]. Sci Transl Med, 2014, 6(263): 263ra159.
18	Marupuru S, Senapati P, Pathadka S, et al. Protective effect of metformin against tuberculosis infections in diabetic patients: an observational study of south Indian tertiary healthcare facility[J]. Braz J Infect Dis, 2017, 21(3): 312-316.
19	Malik F, Mehdi SF, Ali H, et al. Is metformin poised for a second career as an antimicrobial?[J]. Diabetes Metab Res Rev, 2018, 34(4): e2975.
20	Tsoyi K, Jang HJ, Nizamutdinova IT, et al. Metformin inhibits HMGB1 release in LPS-treated RAW264.7 cells and increases survival rate of endotoxaemic mice[J]. Br J Pharmacol, 2011, 162(7): 1498-1508.
21	Kim J, Kwak HJ, Cha JY, et al. Metformin suppresses lipopolysaccharide (LPS)-induced inflammatory response in murine macrophages via activating transcription factor-3 (ATF-3) induction[J]. J Biol Chem, 2014, 289(33): 23246-23255.
22	Sun F, Wang HJ, Liu Z, et al. Safety and efficacy of metformin in systemic lupus erythematosus: a multicentre, randomised, double-blind, placebo-controlled trial[J]. Lancet Rheumatol, 2020, 2(4): e210-e216.
23	Fanouriakis A, Kostopoulou M, Alunno A, et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus[J]. Ann Rheum Dis, 2019, 78(6): 736-745.
24	Jorge A, McCormick N, Lu N, et al. Hydroxychloroquine and mortality among patients with systemic lupus erythematosus in the general population[J]. Arthritis Care Res (Hoboken), 2020. DOI: 10.1002/acr.24255.
25	Wu W, Ma J, Zhou Y, et al. Mortality risk prediction in lupus patients complicated with invasive infection in the emergency department: LUPHAS score[J]. Ther Adv Musculoskelet Dis, 2019, 11: 1759720X1988555.
26	Zhang L, Geng S, Qian L, et al. Multidisciplinary care in patients with systemic lupus erythematosus: a randomized controlled trial in China[J]. Int J Clin Pharm, 2019, 41(5): 1247-1255.
27	Garnett JP, Baker EH, Naik S, et al. Metformin reduces airway glucose permeability and hyperglycaemia-induced Staphylococcus aureus load independently of effects on blood glucose[J]. Thorax, 2013, 68(9): 835-845.
28	Lin SY, Tu HP, Lu PL, et al. Metformin is associated with a lower risk of active tuberculosis in patients with type 2 diabetes[J]. Respirology, 2018(23): 1063-1073.
29	Xun YH, Zhang YJ, Pan QC, et al. Metformin inhibits hepatitis B virus protein production and replication in human hepatoma cells[J]. J Viral Hepat, 2014, 21(8): 597-603.
30	Patkee WR, Carr G, Baker EH, et al. Metformin prevents the effects of Pseudomonas aeruginosa on airway epithelial tight junctions and restricts hyperglycaemia-induced bacterial growth[J]. J Cell Mol Med, 2016, 20(4): 758-764.
31	Shaw RJ, Lamia KA, Vasquez D, et al. The kinase LKB₁ mediates glucose homeostasis in liver and therapeutic effects of metformin[J]. Science, 2005, 310(5754): 1642-1646.
32	Zhang CS, Li M, Ma T, et al. Metformin activates AMPK through the lysosomal pathway[J]. Cell Metab, 2016, 24(4): 521-522.
33	Zhou G, Myers R, Li Y, et al. Role of AMP-activated protein kinase in mechanism of metformin action[J]. J Clin Invest, 2001, 108(8): 1167-1174.

Indicator	With infection （n=49）	Without infection （n=91）	P value
Female/n(%)	45 (91.8)	86 (94.5)	0.539
Age/year	35.1±12.8	32.1±10.9	0.255
Disease duration/year	5.2±5.3	4.5±3.7	0.779
BMI/(kg·m^－2)	23.5±4.0	22.7±3.5	0.221
Complication/n(%)	10 (20.4)	21 (23.1)	0.717
Lupus nephritis	6 (12.2)	16 (17.6)	0.408
Immune thrombocytopenia	2 (4.1)	3 (3.3)	0.811
Antiphospholipid syndrome	1 (2.0)	1 (1.1)	0.666
Pulmonary hypertension	1 (2.0)	1 (1.1)	0.666
SELENA-SLEDAI	2.4±1.8	2.7±1.6	0.481
Laboratory result
White blood cell/(×10⁹·L^－1)	6.0 (4.7, 8.0)	5.4 (4.2, 7.3)	0.270
Neutrophil/(×10⁹·L^－1)	4.2±2.2	3.9±1.9	0.428
Lymphocyte/(×10⁹·L^－1)	1.4 (1.0, 1.9)	1.5 (1.1, 2.0)	0.317
Hemoglobin/(g·L^－1)	127.3±14.0	125.6±21.7	0.810
Platelet/(×10⁹·L^－1)	223.5 (159.5, 270.0)	213.0 (162.8, 263.5)	0.814
ESR/(mm·h^－1)	11.0 (7.0, 28.0)	13.0 (5.3, 30.0)	0.641
CRP/(mg·L^－1)	2.5 (2.0, 4.3)	2.5 (1.0, 4.0)	0.694
GPT /(U·L^－1)	16.4±11.7	20.5±16.2	0.203
Serum creatinine/ (μmol·L^－1)	57.9±9.4	57.9±12.6	0.784
Anti-dsDNA antibody/ (IU·mL^－1)	22.0 (4.3, 53.1)	30.0 (14.7, 87.5)	0.176
Complement 3/(g·L^－1)	0.8±0.3	0.8±0.2	0.782
Complement 4/(g·L^－1)	0.2±0.0	0.1±0.1	0.161
IgG/(g·L^－1)	13.9±4.8	14.5±5.5	0.703
IgM/(g·L^－1)	0.7±1.3	0.5±0.6	0.856
IgA/(g·L^－1)	2.9±2.1	2.3±1.4	0.171
Medication
Prednisone/(mg·d^－1)	10.0 (7.5, 15.0)	10.0 (6.3, 15.0)	0.914
Hydroxychloroquine/n (%)	44 (89.8)	82 (90.1)	0.539
Immunosuppressants/n (%)	33 (67.4)	60 (65.9)	0.866
Azathioprine	2 (4.1)	7 (7.7)	0.406
Mycophenolate	18 (36.7)	29 (31.9)	0.561
Calcineurin inhibitor	4 (8.2)	6 (6.6)	0.731
Methotrexate	8 (16.3)	16 (17.6)	0.851
Leflunomide	1 (2.0)	2 (2.2)	0.951
Metformin/n(%)	17 (34.7)	50 (65.9)	0.022

Indicator	With infection （n=49）	Without infection （n=91）	P value
Female/n(%)	45 (91.8)	86 (94.5)	0.539
Age/year	35.1±12.8	32.1±10.9	0.255
Disease duration/year	5.2±5.3	4.5±3.7	0.779
BMI/(kg·m^－2)	23.5±4.0	22.7±3.5	0.221
Complication/n(%)	10 (20.4)	21 (23.1)	0.717
Lupus nephritis	6 (12.2)	16 (17.6)	0.408
Immune thrombocytopenia	2 (4.1)	3 (3.3)	0.811
Antiphospholipid syndrome	1 (2.0)	1 (1.1)	0.666
Pulmonary hypertension	1 (2.0)	1 (1.1)	0.666
SELENA-SLEDAI	2.4±1.8	2.7±1.6	0.481
Laboratory result
White blood cell/(×10⁹·L^－1)	6.0 (4.7, 8.0)	5.4 (4.2, 7.3)	0.270
Neutrophil/(×10⁹·L^－1)	4.2±2.2	3.9±1.9	0.428
Lymphocyte/(×10⁹·L^－1)	1.4 (1.0, 1.9)	1.5 (1.1, 2.0)	0.317
Hemoglobin/(g·L^－1)	127.3±14.0	125.6±21.7	0.810
Platelet/(×10⁹·L^－1)	223.5 (159.5, 270.0)	213.0 (162.8, 263.5)	0.814
ESR/(mm·h^－1)	11.0 (7.0, 28.0)	13.0 (5.3, 30.0)	0.641
CRP/(mg·L^－1)	2.5 (2.0, 4.3)	2.5 (1.0, 4.0)	0.694
GPT /(U·L^－1)	16.4±11.7	20.5±16.2	0.203
Serum creatinine/ (μmol·L^－1)	57.9±9.4	57.9±12.6	0.784
Anti-dsDNA antibody/ (IU·mL^－1)	22.0 (4.3, 53.1)	30.0 (14.7, 87.5)	0.176
Complement 3/(g·L^－1)	0.8±0.3	0.8±0.2	0.782
Complement 4/(g·L^－1)	0.2±0.0	0.1±0.1	0.161
IgG/(g·L^－1)	13.9±4.8	14.5±5.5	0.703
IgM/(g·L^－1)	0.7±1.3	0.5±0.6	0.856
IgA/(g·L^－1)	2.9±2.1	2.3±1.4	0.171
Medication
Prednisone/(mg·d^－1)	10.0 (7.5, 15.0)	10.0 (6.3, 15.0)	0.914
Hydroxychloroquine/n (%)	44 (89.8)	82 (90.1)	0.539
Immunosuppressants/n (%)	33 (67.4)	60 (65.9)	0.866
Azathioprine	2 (4.1)	7 (7.7)	0.406
Mycophenolate	18 (36.7)	29 (31.9)	0.561
Calcineurin inhibitor	4 (8.2)	6 (6.6)	0.731
Methotrexate	8 (16.3)	16 (17.6)	0.851
Leflunomide	1 (2.0)	2 (2.2)	0.951
Metformin/n(%)	17 (34.7)	50 (65.9)	0.022

Factor	β value	Standard error	Wald value	P value	OR (95%CI)
Gender	0.176	0.818	0.046	0.829	1.193 (0.240－5.930)
Age	0.018	0.017	1.123	0.289	1.018 (0.985－1.053)
SELENA-SLEDAI	0.125	0.133	0.876	0.349	1.133 (0.872－1.471)
Neutrophil	0.025	0.110	0.053	0.818	1.026 (0.827－1.272)
Prednisone	-0.022	0.035	0.381	0.537	0.979 (0.914－1.048)
Use of hydroxychloroquine	1.014	0.826	1.506	0.220	2.755 (0.546－13.905)
Use of metformin	-0.860	0.404	4.536	0.033	0.423 (0.192－0.934)

Factor	β value	Standard error	Wald value	P value	OR (95%CI)
Gender	0.176	0.818	0.046	0.829	1.193 (0.240－5.930)
Age	0.018	0.017	1.123	0.289	1.018 (0.985－1.053)
SELENA-SLEDAI	0.125	0.133	0.876	0.349	1.133 (0.872－1.471)
Neutrophil	0.025	0.110	0.053	0.818	1.026 (0.827－1.272)
Prednisone	-0.022	0.035	0.381	0.537	0.979 (0.914－1.048)
Use of hydroxychloroquine	1.014	0.826	1.506	0.220	2.755 (0.546－13.905)
Use of metformin	-0.860	0.404	4.536	0.033	0.423 (0.192－0.934)

Indicator	Metformin (n=17)	Placebo (n=32)	P value
Female/n(%)	15 (88.2)	30 (93.8)	0.502
Age/year	36.6±14.4	34.3±12.0	0.634
Disease duration/year	5.2±5.8	5.1±5.0	0.846
BMI/(kg·m^－2)	22.1±3.1	24.3±4.1	0.056
SELENA-SLEDAI	2.4±1.7	3.1±2.1	0.184
Laboratory result
White blood cell/ (×10⁹·L^－1)	5.9 (4.52, 7.5)	6.0 (4.5, 7.3)	0.852
Neutrophil/(×10⁹·L^－1)	4.7±2.3	5.5±1.9	0.446
Platelet/(×10⁹·L^－1)	223.5 (159.5, 267.3)	230.5 (176.5, 276.8)	0.582
ESR/(mm·h^－1)	25.5 (10.5, 44.5)	17.0 (7.3, 30.8)	0.185
CRP/(mg·L^－1)	2.5 (2.4, 6.4)	4.5 (2.5, 8.9)	0.075
Anti-dsDNA antibody/ (IU·mL^－1)	23.0 (4.5, 34.1)	22.0 (3.0, 62.2)	0.622
Complement 3/(g·L^－1)	0.9±0.3	0.8±0.2	0.087
Complement 4/(g·L^－1)	0.2±0.1	0.2±0.1	0.112
IgG/(g·L^－1)	3.3±1.9	2.9±2.5	0.997
IgM/(g·L^－1)	17.9±10.0	15.8±7.5	0.331
IgA/(g·L^－1)	1.2±0.6	1.0±0.4	0.746
Medication
Prednisone/(mg·d^－1)	5.0 (3.8, 7.5)	6.9 (5.0, 12.5)	0.084
Hydroxychloroquine/n (%)	15 (88.2)	29 (90.6)	0.793
Immunosuppressants/n (%)	13 (76.5)	20 (62.5)	0.321
Infection duration/d	7.0 (6.0, 11.8)	10.0 (7.0, 21.8)	0.034
Infection/n (%)			0.466
Severe infection	1 (5.9)	4 (12.5)
Mild infection	16 (94.1)	28 (87.5)

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

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

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