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The authors review the use of metformin among patients with type 2 diabetes and COVID-19. Metformin can reduce inflammation, act as an antioxidant, and alter the composition of gut microbiota. These properties may help to combat the cytokine storm seen in patients with diabetes and COVID-19. Previous studies have shown that metformin has benefits in both lung disease and sepsis, including a reduction in the mortality risk. Metformin use has been associated with improved outcomes among patients with type 2 diabetes and COVID-19, in part due to the effect on improved glycemic control. In addition, select studies have shown other potential benefits of metformin use, such as reduced interleukin-6 levels and increased albumin levels. Most notably, metformin use was shown to be associated with a fourfold reduction in the risk of in-hospital mortality.
Metformin does not appear to be harmful in patients with type 2 diabetes and COVID-19 and may have some protective and beneficial effects.
This abstract is available on the publisher's site.
Most of the expert consensus to date have suggested avoiding metformin in patients with diabetes and coronavirus disease-19 (COVID-19), due to an anticipated fear of lactic acidosis in the background of multi-organ dysfunction including hepatic and renal impairment [1-6]. However, these earlier advisories were made in the absence of studies conducted with anti-diabetic drugs in patients with diabetes and COVID-19.
Historically, host-directed anti-viral properties of metformin were utilized during the treatment of influenza outbreak in Philippines in 1949 . Proguanil, an immediate predecessor of metformin is still used in the prevention and treatment of malaria. Serendipitously, both these drugs were found to have a glucose lowering properties since the 1940s . This ability of metformin was further pursued by French physician Jean Sterne, in the treatment of diabetes in 1957 and is being used for the same in United Kingdom and Europe, since 1958 . United States permitted the use of metformin in diabetes only after an intensive scrutiny in 1995, despite all the reverberations of lactic acidosis associated with phenformin and buformin of the same biguanide family . While both phenformin and buformin were withdrawn in the 1970s, metformin came out to become the first line anti-diabetic drug in the treatment of type 2 diabetes, after passing a series of tests and trials, including the epic United Kingdom Prospective Diabetes Study-34 . Interestingly, the historical use of metformin during influenza and malaria outbreak is somehow analogous to the recent use of anti-influenza and anti-malarial drug as a repurposed agent in the treatment of COVID-19, in the absence of any licensed agent.