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Effects of metformin on acute respiratory distress syndrome in preclinical studies: a systematic review and meta-analysis

Wang et al., Frontiers in Pharmacology, doi:10.3389/fphar.2023.1215307
Sep 2023  
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Metformin for COVID-19
3rd treatment shown to reduce risk in July 2020, now with p < 0.00000000001 from 99 studies.
No treatment is 100% effective. Protocols combine treatments.
5,100+ studies for 112 treatments. c19early.org
Systematic review and meta-analysis of 15 non-COVID-19 preclinical studies of metformin for acute respiratory distress syndrome (ARDS) or acute lung injury (ALI), showing that metformin inhibits pulmonary inflammation and oxidative stress, minimizes lung injury, and improves survival in animal models.
12 preclinical studies support the efficacy of metformin for COVID-19:
A systematic review and meta-analysis of 15 non-COVID-19 preclinical studies showed that metformin inhibits pulmonary inflammation and oxidative stress, minimizes lung injury, and improves survival in animal models of acute respiratory distress syndrome (ARDS) or acute lung injury (ALI)10. Metformin inhibits SARS-CoV-2 in vitro7,8, minimizes LPS-induced cytokine storm in a mouse model9, minimizes lung damage and fibrosis in a mouse model of LPS-induced ARDS6, may protect against SARS-CoV-2-induced neurological disorders5, may be beneficial via inhibitory effects on ORF3a-mediated inflammasome activation11, reduces UUO and FAN-induced kidney fibrosis6, increases mitochondrial function and decreases TGF-β-induced fibrosis, apoptosis, and inflammation markers in lung epithelial cells6, may reduce inflammation, oxidative stress, and thrombosis via regulating glucose metabolism1, attenuates spike protein S1-induced inflammatory response and α-synuclein aggregation4, and may improve outcomes via modulation of immune responses with increased anti-inflammatory T lymphocyte gene expression and via enhanced gut microbiota diversity12.
Wang et al., 28 Sep 2023, China, peer-reviewed, 3 authors. Contact: wwwlll838940@163.com.
This PaperMetforminAll
Effects of metformin on acute respiratory distress syndrome in preclinical studies: a systematic review and meta-analysis
Liu Wang, Yan-Fen Tian, Wen-Qing Deng
Frontiers in Pharmacology, doi:10.3389/fphar.2023.1215307
Introduction: In this study, we conducted a systematic review and meta-analysis to judge the effects of metformin on acute respiratory distress syndrome (ARDS) in a comprehensive and quantitative manner. Methods: We included studies that tested the effects of metformin on ALI or ARDS in in vivo studies. We excluded literature from which data could not be extracted or obtained. Electronic search was conducted to retrieve relevant literature from public databases, including PubMed, Web of Science, Embase, Scopus, and the Cochrane Central Register of Controlled Trials (inception to July 2023). Moreover, ProQuest Dissertations and Theses Global, Google Scholar, and Baidu scholar were inquired. Retrieved literature was screened and evaluated by pairs of reviewers independently according to pre-stated criteria. The Systematic Review Center for Laboratory Animal Experimentation risk of bias tool was used to evaluate the methodological quality of eligible literature. No restriction was exerted on publication status or language. Results: Fifteen preclinical studies were analyzed in this meta-analysis. Pooled results showed metformin effectively decreased pulmonary wet-to-dry weight ratios [SMD = -2.67 (-3.53 to -1.81), I 2 = 56.6%], protein content [SMD = -3.74 (-6.76 to -0.72), I 2 = 86.7%] and neutrophils [SMD = -3.47 (-4.69 to -2.26), I 2 = 0%] in BALF, pulmonary malondialdehyde [SMD = -1.98 (-3.77 to -0.20), I 2 = 74.2%] and myeloperoxidase activity [SMD = -3.15 (-4.79 to -1.52), I 2 = 74.5%], lung injury scores [SMD = -4.19 (-5.65 to -2.74), I 2 = 69.1%], and mortality at 24 h [RR = 0.43 (0.24-0.76), I 2 = 0%] as well as 48 and 72 h. Conclusion: Metformin inhibited pulmonary inflammation and oxidative stress and improved experimental lung injury and survival rates in animal models of ARDS. Results from randomized controlled trials are needed.
Author contributions LW and Y-FT conceived and designed the study. W-QD and LW performed the literature search. LW and Y-FT selected trials and extracted data. LW and W-QD assessed the risk of bias of trials. LW and W-QD analyzed the data. LW and W-QD wrote the manuscript. Y-FT revised the manuscript. All authors contributed to the article and approved the submitted version. Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Publisher's note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors, and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Supplementary material The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fphar.2023.1215307/ full#supplementary-material
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Electronic search was ' 'conducted to retrieve relevant literature from public databases, including PubMed, Web of ' 'Science, Embase, Scopus, and the Cochrane Central Register of Controlled Trials (inception to ' 'July 2023). Moreover, ProQuest Dissertations and Theses Global, Google Scholar, and Baidu ' 'scholar were inquired. Retrieved literature was screened and evaluated by pairs of reviewers ' 'independently according to pre-stated criteria. The Systematic Review Center for Laboratory ' 'Animal Experimentation risk of bias tool was used to evaluate the methodological quality of ' 'eligible literature. No restriction was exerted on publication status or ' 'language.</jats:p><jats:p><jats:bold>Results:</jats:bold> Fifteen preclinical studies were ' 'analyzed in this meta-analysis. 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