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Correlation between metformin use and mortality in acute respiratory failure: a retrospective ICU cohort study

Yang et al., Frontiers in Pharmacology, doi:10.3389/fphar.2025.1584230, Aug 2025
https://c19early.org/yang20.html
Metformin for COVID-19
3rd treatment shown to reduce risk in July 2020, now with p < 0.00000000001 from 107 studies.
No treatment is 100% effective. Protocols combine treatments.
6,100+ studies for 180 treatments. c19early.org
Retrospective 1,429 ICU patients with acute respiratory failure showing significantly reduced mortality with metformin use.
Yang et al., 26 Aug 2025, retrospective, China, peer-reviewed, 6 authors. Contact: hliang_1022@163.com, weiweieric0405@163.com.
Correlation between metformin use and mortality in acute respiratory failure: a retrospective ICU cohort study
Yunlin Yang, Jinfeng Liu, Yi Hou, Yuxun Wei, Liang Huang, Wei Wei
Frontiers in Pharmacology, doi:10.3389/fphar.2025.1584230
Background: The aim of this study was to investigate the association of metformin use with the risk of in-hospital mortality and prognosis in acute respiratory failure (ARF) patients admitted to the intensive care unit (ICU). Methods: We conducted a retrospective cohort study using the MIMIC-IV database. Patients were categorized into metformin and non-metformin groups based on medication exposure. Primary outcomes were in-hospital and ICU mortality, while 30-day and 90-day all-cause mortality served as secondary endpoints. We applied Kaplan-Meier survival curves, Cox proportional hazards models, and logistic regression to assess associations. Propensity score matching (PSM) and machine learning algorithms were used for confounder adjustment and feature selection. Results: After PSM, 1,429 patients with ARF were included (374 metformin users; 1,055 non-users). Multivariate logistic regression revealed that metformin use was associated with significantly reduced in-hospital mortality (OR = 0.202, 95% CI: 0.123-0.317, p < 0.001) and ICU mortality (OR = 0.245, 95% CI: 0.142-0.399, p < 0.001). Cox models showed consistent reductions in 30-day (HR = 0.199, 95% CI: 0.124-0.320, p < 0.001) and 90-day (HR = 0.230, 95% CI: 0.150-0.352, p < 0.001) mortality. Kaplan-Meier curves confirmed better survival in the metformin group (p < 0.001). Subgroup analyses supported a consistent protective effect of metformin across most patient strata. Conclusion: Metformin use was significantly associated with decreased shortterm mortality among ICU patients with ARF. These findings suggest that metformin, beyond its glucose-lowering effects, may offer survival benefits in critically ill populations. Clinicians should consider the potential role of metformin when managing ICU patients with type 2 diabetes and ARF. Further prospective studies are warranted to confirm these findings and optimize clinical application strategies.
Author contributions YY: Conceptualization, Data curation, Formal Analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writingoriginal draft, Writingreview and editing. JL: Investigation, Software, Writingreview and editing. YH: Supervision, Validation, Writingoriginal draft. YW: Conceptualization, Investigation, Software, Writingreview and editing. LH: Conceptualization, Data curation, Writingoriginal draft, Writingreview and editing. WW: Data curation, Formal Analysis, Resources, Writingoriginal draft, Writingreview and editing. expertise and insights greatly contributed to the design and execution of this research. We also thank the developers and maintainers of the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database for providing open access to high-quality clinical data, which was essential for the completion of this study. 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. Generative AI statement The author(s) declare that no Generative AI was used in the creation of this manuscript. Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors..
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DOI record: { "DOI": "10.3389/fphar.2025.1584230", "ISSN": [ "1663-9812" ], "URL": "http://dx.doi.org/10.3389/fphar.2025.1584230", "abstract": "<jats:sec><jats:title>Background</jats:title><jats:p>The aim of this study was to investigate the association of metformin use with the risk of in-hospital mortality and prognosis in acute respiratory failure (ARF) patients admitted to the intensive care unit (ICU).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We conducted a retrospective cohort study using the MIMIC-IV database. Patients were categorized into metformin and non-metformin groups based on medication exposure. Primary outcomes were in-hospital and ICU mortality, while 30-day and 90-day all-cause mortality served as secondary endpoints. We applied Kaplan–Meier survival curves, Cox proportional hazards models, and logistic regression to assess associations. Propensity score matching (PSM) and machine learning algorithms were used for confounder adjustment and feature selection.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>After PSM, 1,429 patients with ARF were included (374 metformin users; 1,055 non-users). Multivariate logistic regression revealed that metformin use was associated with significantly reduced in-hospital mortality (OR = 0.202, 95% CI: 0.123–0.317, p &amp;lt; 0.001) and ICU mortality (OR = 0.245, 95% CI: 0.142–0.399, p &amp;lt; 0.001). Cox models showed consistent reductions in 30-day (HR = 0.199, 95% CI: 0.124–0.320, p &amp;lt; 0.001) and 90-day (HR = 0.230, 95% CI: 0.150–0.352, p &amp;lt; 0.001) mortality. Kaplan–Meier curves confirmed better survival in the metformin group (p &amp;lt; 0.001). Subgroup analyses supported a consistent protective effect of metformin across most patient strata.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Metformin use was significantly associated with decreased short-term mortality among ICU patients with ARF. These findings suggest that metformin, beyond its glucose-lowering effects, may offer survival benefits in critically ill populations. Clinicians should consider the potential role of metformin when managing ICU patients with type 2 diabetes and ARF. Further prospective studies are warranted to confirm these findings and optimize clinical application strategies.</jats:p></jats:sec>", "alternative-id": [ "10.3389/fphar.2025.1584230" ], "article-number": "1584230", "author": [ { "affiliation": [], "family": "Yang", "given": "Yunlin", "sequence": "first" }, { "affiliation": [], "family": "Liu", "given": "Jinfeng", "sequence": "additional" }, { "affiliation": [], "family": "Hou", "given": "Yi", "sequence": "additional" }, { "affiliation": [], "family": "Wei", "given": "Yuxun", "sequence": "additional" }, { "affiliation": [], "family": "Huang", "given": "Liang", "sequence": "additional" }, { "affiliation": [], "family": "Wei", "given": "Wei", "sequence": "additional" } ], "container-title": "Frontiers in Pharmacology", "container-title-short": "Front. 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Late treatment
is less effective
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