Metformin is a medication that is the first line of treatment for type 2 diabetes. It is also sometimes used to prevent type 2 diabetes in people with diabetes, and also as a treatment for polycystic ovary sydrome (PCOS) in women. We know that severe COVID-19 infections are characterized by a profound inflammatory response, and we know that metformin decreases inflammation, particularly in females.
So, the question has been asked: could metformin use be associated with better outcomes from a severe coronavirus infection?
The study evaluated a US claims database, evaluating adults with type 2 diabetes or obesity who had been hospitalized with COVID-19 between January and June 2020. They defined ‘metformin use’ as having at least 90 days of metformin prescription from 12 months prior to COVID-19 diagnosis.
After controlling for other factors (and across all multivariate analyses), they found that metformin use was associated with 22% reduction in mortality, in women only.
Outside of COVID-19, metformin has been shown to decrease levels of inflammatory cytokines IL-6 and TNF-alpha, more so in women than in men. Metformin has also been shown to increase IL-10, an anti-inflammatory cytokine, in females more than males. While these cytokines were not measured in this database (nor are they measured in routine clinical practice), the hypothesis is that these may be the reasons why metformin use was associated with lower mortality from COVID-19. Note that metformin is routinely stopped when a person is very ill (of any cause), suggesting that the benefits of metformin begin prior to hospitalization.
There are major limitations to this study: we know nothing about how much/often patients were actually taking the metformin prescribed. It is a retrospective analysis which can always be subject to biases and confounding (ie other factors that may be responsible for the differences seen). The study has also not been peer reviewed for publication.
BOTTOM LINE : Metformin has anti-inflammatory properties that may be of benefit in the context of COVID-19. However, the quality of this data is relatively weak and should be interpreted with a big grain of salt. It is by no means any indication that metformin should be prescribed for anything other than for its usual recommended reasons. We look forward to more data on this topic.
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