Metformin Use Before COVID-19 Drastically Reduces Mortality Risk

Anath Shalev, MD

Research from a team at the University of Alabama at Birmingham (UAB) provides information that suggests use of metformin before a diagnosis of coronavirus disease 2019 (COVID-19) was linked to dramatic reductions in mortality.

A retrospective review of data from electronic health records from an Alabama hospital, results of the study suggests patients using metformin before a diagnosis of COVID-19 only had a third of the mortality risk of their counterparts with no reported use of the common diabetes medication.

"This beneficial effect remained, even after correcting for age, sex, race, obesity, and hypertension or chronic kidney disease and heart failure," said lead investigator Anath Shalev, MD, director of UAB's Comprehensive Diabetes Center, in a statement. "Since similar results have now been obtained in different populations from around the world—including China, France and a UnitedHealthcare analysis—this suggests that the observed reduction in mortality risk associated with metformin use in subjects with Type 2 diabetes and COVID-19 might be generalizable.”

Throughout the COVID-19 pandemic, many of the most discussed studies and research pertained to racial or ethnic disparities in outcomes and contracting the virus. With an interest in how specific characteristics influence risk in populations considered at-risk, investigators designed the current study with the aim of evaluating these trends through electronic health record data from a UAB Hospital from February 25, 2020 through June 22, 2020.

During the study period, 24,722 hospital subjects tested negative for COVID-19 and 604 subjects tested positive, yielding a positivity rate of 2.4%. Investigators noted the low positivity rate was most likely caused by the testing of asymptomatic hospital staff and patients coming in for elective procedures. Of note, when examining those who tested positive for COVID-19, 70% had preexisting hypertension, 61% were obese, and 40% had diabetes.

The primary outcome of the analysis was mortality and the effects of patient characteristics and comorbidities. Investigators noted patients were classified as positive or negative for COVID-19 based on RT-PCR results from SARS-CoV-2 viral nucleic acid testing in respiratory specimens. To minimize bias, investigators' only inclusion criteria was completing testing within the study period and the only exclusion criteria was having complete outcomes data.

Upon analysis, results suggested Black Americans were more than twice as likely to contract COVID-19 (OR, 2.6; 95% CI, 2.19-3.10; P <.0001). To further outline racial disparities in contracting COVID-19, investigators pointed out only 36% of COVID-19 positive patients were white, despite making up 56% of those who tested negative.

Additional factors associated with contracting COVID-19 included obesity (OR 1.93; 95% CI, 1.64–2.28; P <.0001), hypertension (OR 2.46; 95% CI, 2.07–2.93; P <.0001), and diabetes (OR 2.11; 95% CI, 1.78–2.48; P <.0001). When assessing for independent risk factors associated with increased mortality, investigators found diabetes was associated with 3 times greater risk of mortality from COVID-19 (OR, 3.62; 95% CI, 2.11-6.2; P <.0001).

When assessing the effect of using insulin nor metformin prior to the study period, insulin did not influence mortality risk but metformin was associated with significant reductions in odds of mortality (OR, 0.38; 95% CI, 0.17-0.87; P=.0221). In patients with diabetes, this effect appeared even greater (OR, 0.33; 95% CI 0.13–0.84; P=.0210). In analyses excluding patients with chronic kidney disease or chronic heart failure, metformin was still associated with a significant reduction in mortality risk (OR, 0.17; 95% CI, 0.04-0.79; P=.0231).

"These results suggest that, while diabetes is an independent risk factor for COVID-19-related mortality," Shalev added. “This risk is dramatically reduced in subjects taking metformin—raising the possibility that metformin may provide a protective approach in this high-risk population."

This study, “Metformin Use Is Associated With Reduced Mortality in a Diverse Population With COVID-19 and Diabetes,” was published in Frontiers of Endocrinology.