In an observational study published in ‘The Lancet’ by researchers at the University of Minnesota Medical School and United Health Group observed that the commonly used medication for diabetes, metformin, lowers mortality risk in women. This is the first observational study of its kind to report decreased mortality with outpatient metformin use in women with type 2 diabetes or obesity in a large cohort of patients admitted to hospital in the USA for COVID-19, and to describe a sex difference in this response to metformin. Metformin has cytokine-reducing, sex-specific immunomodulatory effects and anti-inflammatory effects that have been shown to reduce levels of IL-6 and TNFα that appear to make COVID-19 worse in women.

      The retrospective cohort analysis based on de-identified patient data from United Health Group analyzed about 6,000 individuals with type 2 diabetes or obesity who were hospitalized with COVID-19 and assessed whether or not metformin use was associated with decreased mortality. Researchers observed that women with diabetes or obesity, who were hospitalized for COVID-19 disease and who had filled a 90-day metformin prescription before hospitalization, had a 21% to 24% reduced likelihood of mortality compared to similar women not taking the medication.

     Metformin use was not associated with significantly decreased mortality in the overall sample of men and women. Metformin was associated with decreased mortality in women by Cox proportional hazards (HR 0·785, 95% CI 0·650–0·951) and propensity matching (OR 0·759, 95% CI 0·601–0·960, p=0·021). There was no significant reduction in mortality among men.

      The outcome suggests that metformin was significantly associated with reduced mortality in women with obesity or type 2 diabetes who were admitted to hospital for COVID-19. The results provide new directions for research against COVID-19. Prospective studies are needed to understand mechanism and causality. If findings are reproducible, metformin could be widely distributed for prevention of COVID-19 mortality, because it is safe and inexpensive. The team submitted an investigational new drug application to the FDA for use of metformin for COVID-19 treatment and prevention and the FDA approved this application.