Metformin for treatment of acute COVID-19: systematic review of clinical trial data against SARS-CoV-2
Objective: Observational and preclinical data suggest metformin may prevent severe COVID-19 outcomes. We conducted a systematic review of randomized, placebo-controlled clinical trials of metformin treatment for COVID-19 to determine whether metformin affects clinical or laboratory outcomes in individuals infected with SARS-CoV-2 and a structured summary of pre-clinical data.
Research Design and Methods: Two independent reviewers searched PubMed, Scopus, Cochrane Covid-19 Study Register, and ClinicalTrials.gov on February 1, 2023 with no date restrictions for trials which randomized adults with COVID-19 to metformin versus control and assessed clinical and/or laboratory outcomes of interest. The Cochrane Risk of Bias 2 tool was used to assess bias. The synthesis plan was developed a priori and was guided by SWiM guidelines. Summary tables and narrative synthesis were used. (PROSPERO 2022 CRD42022349896)
Results: Three randomized trials met inclusion criteria. Two of the trials found metformin improved clinical outcomes (prevented need for oxygen; and prevented need for acute healthcare use), and the third trial enrolled a larger portion of adults with diabetes but did show a direction of benefit similar to the other trials in the per-protocol group. The largest trial enrolled during the delta and omicron waves and included vaccinated individuals. The certainty of evidence that metformin prevents healthcare utilization due to COVID-19 was moderate per GRADE criteria. Many preclinical studies have found metformin to be effective against SARS-CoV-2. Limitations include inclusion of only three trials and heterogeneity between trials.
Conclusions: Future trials will help define the role of metformin in COVID-19 treatment guidelines.