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

Yin Li; Xue Yang; Peijing Yan; Tong Sun; Zhi Zeng; Sheyu Li

doi:10.3389/fmed.2021.704666

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

Front Med (Lausanne). 2021 Aug 19:8:704666. doi: 10.3389/fmed.2021.704666. eCollection 2021.

Authors

Yin Li¹, Xue Yang², Peijing Yan², Tong Sun³, Zhi Zeng⁴, Sheyu Li^{5

6}

Affiliations

¹ "Double First-Class" Construction Office, West China Hospital, Sichuan University, Chengdu, China.
² Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
³ Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, China.
⁴ Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China.
⁵ Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China.
⁶ Department of Guideline and Rapid Recommendation, Chinese Evidence-Based Medicine Center, Cochrane China Center and MAGIC China Center, West China Hospital, Sichuan University, Chengdu, China.

Abstract

Importance/Background: 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. Methods: 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. Results: 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; I ² = 67.9%] and 27% lower hospitalization rate (pooled OR, 0.73; 95% CI, 0.53-1.00; I ² = 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; I ² = 0.0% for intubation and OR, 2.04; 95% CI, 0.65-6.34; I ² = 79.4% for deterioration of COVID-19), respectively. Conclusions: 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. Study Registration: The study was registered on the PROSPERO on Feb 23, 2021 (CRD42021238722).

Keywords: COVID-19; deterioration; hospitalization; intubation; metformin; mortality.

Publication types

Systematic Review