Metformin Use Is Associated with Decreased Mortality in COVID-19 Patients with Diabetes: Evidence from Retrospective Studies and Biological Mechanism
Tahmina Nasrin Poly, Md. Mohaimenul Islam, Yu-Chuan (jack) Li, Ming-Chin Lin, Min-Huei Hsu, Yao-Chin Wang
Journal of Clinical Medicine, doi:10.3390/jcm10163507
Background and Aims: The coronavirus disease 2019 (COVID-19) increases hyperinflammatory state, leading to acute lung damage, hyperglycemia, vascular endothelial damage, and a higher mortality rate. Metformin is a first-line treatment for type 2 diabetes and is known to have anti-inflammatory and immunosuppressive effects. Previous studies have shown that metformin use is associated with decreased risk of mortality among patients with COVID-19; however, the results are still inconclusive. This study investigated the association between metformin and the risk of mortality among diabetes patients with COVID-19. Methods: Data were collected from online databases such as PubMed, EMBASE, Scopus, and Web of Science, and reference from the most relevant articles. The search and collection of relevant articles was carried out between 1 February 2020, and 20 June 2021. Two independent reviewers extracted information from selected studies. The randomeffects model was used to estimate risk ratios (RRs), with a 95% confidence interval. Results: A total of 16 studies met all inclusion criteria. Diabetes patients given metformin had a significantly reduced risk of mortality (RR, 0.65; 95% CI: 0.54-0.80, p < 0.001, heterogeneity I 2 = 75.88, Q = 62.20, and τ 2 = 0.06, p < 0.001) compared with those who were not given metformin. Subgroup analyses showed that the beneficial effect of metformin was higher in the patients from North America (RR, 0.43; 95% CI: 0.26-0.72, p = 0.001, heterogeneity I 2 = 85.57, Q = 34.65, τ 2 = 0.31) than in patients from Europe (RR, 0.67; 95% CI: 0.47-0.94, p = 0.02, heterogeneity I 2 = 82.69, Q = 23.11, τ 2 = 0.10) and Asia (RR, 0.90; 95% CI: 0.43-1.86, p = 0.78, heterogeneity I 2 = 64.12, Q = 11.15, τ 2 = 0.40). Conclusions: This meta-analysis shows evidence that supports the theory that the use of metformin is associated with a decreased risk of mortality among diabetes patients with COVID-19. Randomized control trials with a higher number of participants are warranted to assess the effectiveness of metformin for reducing the mortality of COVID-19 patients.
Supplementary Materials: The following are available online at https://www.mdpi.com/article/10.3 390/jcm10163507/s1, Figure S1 : Searching strategy, Figure S2 : Metformin use and the risk of mortality of patients with COVID-19 (Studies included metformin users less than 1000 participants), Figure S3 : Metformin use and the risk of mortality of patients with COVID-19 (Studies included metformin users between 1000 and 10,000 participants), Figure S4 : Metformin use and the risk of mortality of patients with COVID-19 (Studies included metformin users more than 10,000 participants).
Conflicts of Interest: The authors declare no conflict of interest.
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'abstract': '<jats:p>Background and Aims: The coronavirus disease 2019 (COVID-19) increases '
'hyperinflammatory state, leading to acute lung damage, hyperglycemia, vascular endothelial '
'damage, and a higher mortality rate. Metformin is a first-line treatment for type 2 diabetes '
'and is known to have anti-inflammatory and immunosuppressive effects. Previous studies have '
'shown that metformin use is associated with decreased risk of mortality among patients with '
'COVID-19; however, the results are still inconclusive. This study investigated the '
'association between metformin and the risk of mortality among diabetes patients with '
'COVID-19. Methods: Data were collected from online databases such as PubMed, EMBASE, Scopus, '
'and Web of Science, and reference from the most relevant articles. The search and collection '
'of relevant articles was carried out between 1 February 2020, and 20 June 2021. Two '
'independent reviewers extracted information from selected studies. The random-effects model '
'was used to estimate risk ratios (RRs), with a 95% confidence interval. Results: A total of '
'16 studies met all inclusion criteria. Diabetes patients given metformin had a significantly '
'reduced risk of mortality (RR, 0.65; 95% CI: 0.54–0.80, p < 0.001, heterogeneity I2 = '
'75.88, Q = 62.20, and τ2 = 0.06, p < 0.001) compared with those who were not given '
'metformin. Subgroup analyses showed that the beneficial effect of metformin was higher in the '
'patients from North America (RR, 0.43; 95% CI: 0.26–0.72, p = 0.001, heterogeneity I2 = '
'85.57, Q = 34.65, τ2 = 0.31) than in patients from Europe (RR, 0.67; 95% CI: 0.47–0.94, p = '
'0.02, heterogeneity I2 = 82.69, Q = 23.11, τ2 = 0.10) and Asia (RR, 0.90; 95% CI: 0.43–1.86, '
'p = 0.78, heterogeneity I2 = 64.12, Q = 11.15, τ2 = 0.40). Conclusions: This meta-analysis '
'shows evidence that supports the theory that the use of metformin is associated with a '
'decreased risk of mortality among diabetes patients with COVID-19. Randomized control trials '
'with a higher number of participants are warranted to assess the effectiveness of metformin '
'for reducing the mortality of COVID-19 patients.</jats:p>',
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