Can metformin prevent mortality in COVID-19 infection?

Type 2 diabetes drug – metformin – may improve COVID-19 results.

The SARS-CoV-2 pandemic has spread across the world at an unprecedented rate, affecting every corner of the planet. One of the few positive outcomes is the ability to analyze real-world evidence. The pandemic has generated mountains of data that can be used to further our understanding of this disease. A new study published in The Lancet uses this real-world approach to evidence to discover a potentially life-saving intervention (1). The study looks at whether the use of metformin protects people with type 2 diabetes or obesity from the serious illness often seen when these types of patients contract COVID-19.

The study included a retrospective analysis of an insurance claims database using data from January 1 to June 7, 2020. Patients were included in the analysis if they had been hospitalized for COVID-19 and known to have type 2 diabetes had or obesity. Patients under the age of 18 or patients with type 1 diabetes were excluded. Enrolled patients were classified as metformin users if they had claims to metformin worth at least 90 days in the 12 months prior to their COVID diagnosis. The main result measured was hospital mortality.

The researchers performed a series of regression analyzes that compared the results for metformin users with those who did not use metformin. The models used controlled a number of other potentially relevant variables to independently isolate the effect of metformin.

A total of 6256 people were included in the analysis. Of these, 2333 were in the metformin group while 3923 were in the non-metformin group. Mortality was higher in the non-metformin group, with 20.2% of these patients dying on admission, compared with 16.9% in the metformin group. However, the results of the regression analysis indicated that the use of metformin did not result in a significantly reduced mortality in the overall cohort. However, a subgroup analysis that split the cohort by gender showed that the use of metformin in women was associated with a significantly reduced mortality (odds ratio = 0.79). These results were consistent across a variety of models and sensitivity analyzes.

The study also discusses why metformin may be beneficial. Both obesity and type 2 diabetes have been linked to chronic inflammatory conditions. This pre-existing chronic inflammation is believed to result in poorer outcomes when patients develop COVID-19. Metformin has been shown to lower levels of an inflammatory mediator called TNF-α, and is much more effective in reducing them in women than in men. This would explain the observation that metformin has greater protective benefits in women.

In essence, this study shows an association and provides a hypothetical explanation for that association. It is not claimed to conclusively show that metformin protects against the serious consequences of COVID-19. In addition, it does not appear to explain any variation in metformin dose or patient compliance. Metformin claims worth 90 days over a 12 month period may not be the most appropriate classification for a metformin user. Further research is needed to determine whether metformin is the cause of the improved results observed here, and if so, whether this protective effect is dose-dependent and whether it only occurs in women, as appears to be the case here.

Written by Michael McCarthy

1. Bramante CT, Ingraham NE, Murray TA, Marmor S., Hovertsen S., Gronski J. et al. Metformin and mortality risk in patients hospitalized with COVID-19: a retrospective cohort analysis. The healthy longevity of the Lancet.

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