AUTHOR=Li Yin , Yang Xue , Yan Peijing , Sun Tong , Zeng Zhi , Li Sheyu 

TITLE=Metformin in Patients With COVID-19: A Systematic Review and Meta-Analysis

JOURNAL=Frontiers in Medicine

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.704666

DOI=10.3389/fmed.2021.704666

ISSN=2296-858X

ABSTRACT=<p><bold>Importance/Background:</bold> The coronavirus disease (COVID-19) pandemic is a critical public health issue. Evidence has shown that metformin favorably influences COVID-19 outcomes. This study aimed to assess the benefits and risks of metformin in COVID-19 patients.</p><p><bold>Methods:</bold> We searched the PubMed, Embase, Cochrane Library, and Chinese Biomedical Literature Database from inception to February 18, 2021. Observational studies assessing the association between metformin use and the outcomes of COVID-19 patients were included. The primary outcome was mortality, and the secondary outcomes included intubation, deterioration, and hospitalization. Random-effects weighted models were used to pool the specific effect sizes. Subgroup analyses were conducted by stratifying the meta-analysis by region, diabetic status, the adoption of multivariate model, age, risk of bias, and timing for adding metformin.</p><p><bold>Results:</bold> We identified 28 studies with 2,910,462 participants. Meta-analysis of 19 studies showed that metformin is associated with 34% lower COVID-19 mortality [odds ratio (OR), 0.66; 95% confidence interval (CI), 0.56–0.78; <italic>I</italic><sup>2</sup> = 67.9%] and 27% lower hospitalization rate (pooled OR, 0.73; 95% CI, 0.53–1.00; <italic>I</italic><sup>2</sup> = 16.8%). However, we did not identify any subgroup effects. The meta-analysis did not identify statistically significant association between metformin and intubation and deterioration of COVID-19 (OR, 0.94; 95% CI, 0.77–1.16; <italic>I</italic><sup>2</sup> = 0.0% for intubation and OR, 2.04; 95% CI, 0.65–6.34; <italic>I</italic><sup>2</sup> = 79.4% for deterioration of COVID-19), respectively.</p><p><bold>Conclusions:</bold> Metformin use among COVID-19 patients was associated with a reduced risk of mortality and hospitalization. Our findings suggest a relative benefit for metformin use in nursing home and hospitalized COVID-19 patients. However, randomized controlled trials are warranted to confirm the association between metformin use and COVID-19 outcomes.</p><p><bold>Study Registration:</bold> The study was registered on the PROSPERO on Feb 23, 2021 (CRD42021238722).</p>