Drug used for type 2 diabetes – metformin – may improve COVID-19 outcomes.
The SARS-CoV-2 pandemic has spread across the globe with unprecedented speed, affecting every corner of the planet. One of the few positives to emerge from this is the opportunities it has provided for analysing real-world evidence. The pandemic has generated mountains of data which can be used to further our understanding of this disease. A new study published in The Lancet exploits this real-world evidence approach in an attempt to discover a potentially life-saving intervention (1). The study examines whether the use of metformin protects people with type-2 diabetes or obesity from the severe disease that has been frequently observed when these types of patients contract COVID-19.
The study involved a retrospective analysis of an insurance claims database, using data from January 1st to June 7th 2020. Patients were included in the analysis if they had been admitted to hospital for COVID-19 and were also known to have either type-2 diabetes or obesity. Patients under the age of 18 or those with type 1 diabetes were excluded. Included patients were classified as metformin users if they had claims for at least 90 days’ worth of metformin in the 12 months prior to their COVID diagnosis. The main outcome measured was in-hospital mortality.
The researchers ran a series of regression analyses which compared the outcomes for metformin users to those who did not use metformin. The models used controlled for a number of other potentially relevant variables in order to independently isolate the effect of metformin.
In total, 6256 individuals 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 during their admission compared to 16.9% of the metformin group. However, the results of the regression analysis suggested that metformin use did not result in significantly reduced mortality in the overall cohort. However, a subgroup analysis that split the cohort by sex found that metformin use in women was associated with a significantly reduced mortality (odds ratio=0.79). These results were consistent across a variety of models and sensitivity analyses.
The study also discusses why metformin may be of benefit. Both obesity and type-2 diabetes are associated with chronic states of inflammation. It is thought that this pre-existing chronic inflammation leads to poorer outcomes when patients contract COVID-19. Metformin has been shown to reduce levels of an inflammatory mediator called TNF-α, and to bring about a much greater reduction in women than in men. This would explain the observation that metformin has a greater protective benefit in women.
Essentially, this study demonstrates an association and provides a hypothetical explanation for that association. It does not claim to conclusively show that metformin protects from severe outcomes in COVID-19. Furthermore, it does not appear to account for variation in metformin dose or patient compliance. Ninety days’ worth of metformin claims in a 12 month period may not be the most appropriate classification of a metformin user. Further research is needed to determine if metformin is the cause of the improved outcomes observed here and if so, whether that protective effect is dose-related 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 risk of mortality in patients hospitalised with COVID-19: a retrospective cohort analysis. The Lancet Healthy Longevity.
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