Abstract
Metformin is the first-line medication for type 2 diabetes, but it also has a long history of improved outcomes in infectious diseases, such as influenza, hepatitis C, and in-vitro assays of zika. In the current Covid-19 pandemic, which has rapidly spread throughout the world, 4 observational studies have been published showing reduced mortality among individuals with home metformin use. There are several potential overlapping mechanisms by which metformin may reduce mortality from Covid-19. Metformin’s past anti-infectious benefits have been both against the infectious agent directly, as well as by improving the underlying health of the human host. It is unknown if the lower mortality suggested by observational studies in patients infected with Covid-19 who are on home metformin is due to direct activity against the virus itself, improved host substrate, or both.
Highlights
Metformin was discovered in the 1920s [1]
We summarize published literature evaluating the relationship between Covid-19 and metformin use
Possible evidence of this effect was seen in a retrospective study by Chen et al: 904 patients with Covid-19 which showed that metformin users had lower interleukin 6 (IL-6) levels compared to nonmetformin users (Table 2) [56]
Summary
Metformin was discovered in the 1920s [1]. In the 1940s-50s, metformin showed benefit when used in influenza infection, and was noted to lower glucose, but not below physiologic levels [2]. Several observational cohort studies have been published in peer review journals showing associations with reduced mortality from Covid-19 among patients already who were already on metformin (Table 1) [8, 9, 11,12,13]. It appears that metformin may be associated with less severe Covid-19 disease, there are no prospective studies published to date. Metformin decreases thrombosis in longterm follow-up, possibly by inhibiting platelet activation factor and mitochondrial DNA (mtDNA) release [63, 64], and may mediate improved cardiovascular outcomes via mechanisms beyond glucose control. Metformin has been associated with reduced pulmonary fibrosis through reduced TGF-beta and VEGF, and resolution of pulmonary
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