Study: Metformin Reduces Risk of Death for Patients with COVID-19, Diabetes

New research suggests that the use of the diabetes drug metformin prior to a coronavirus disease 2019 (COVID-19) diagnosis was associated with a decrease in mortality among patients with type 2 diabetes.

Diabetes is a significant comorbidity for COVID-19, and although the investigators still do not know how metformin improves prognosis in COVID-19, the study findings suggest that the mechanisms may go beyond any expected improvements in glycemic control of obesity. The researchers found that neither body mass index, blood glucose, nor hemoglobin A1C were lower in the metformin users who survived compared with those who died.

“The mechanisms may involve metformin’s previously described anti-inflammatory and anti-thrombotic effects,” said Anath Shalev, MD, leader of the study, in a press release.

The study included 25,326 patients tested for COVID-19 at the tertiary care University of Alabama at Birmingham Hospital between February 25 and June 22, 2020. Of the 604 patients who tested positive, 311 were Black. The primary outcome was mortality in COVID-19-positive patients, and researchers examined the potential association with subject characteristics or comorbidities.

The investigators found that African Americans, who are only 26% of Alabama’s population, accounted for 52% of those who tested positive for COVID-19 and just 30% of those who tested negative. In contrast, 36% of the COVID-19-positive subjects were white, whereas whites made up 56% of those who tested negative. Although these findings reveal a significant racial disparity, the investigators noted that no significant racial difference in mortality was observed once diagnosed with COVID-19.

“In our cohort, being African American appeared to be primarily a risk factor for contracting COVID-19, rather than for mortality,” Shalev said in a press release. “This suggests that any racial disparity observed is likely due to exposure risk and external socioeconomic factors, including access to proper health care.”

Overall mortality for patients with COVID-19 was 11%, and the investigators found that 93% of deaths occurred in patients over 50 years of age, whereas being male or having high blood pressure was associated with a significantly elevated risk of death. Diabetes was associated with a dramatic increase in mortality, with an odds ratio of 3.62. Notably, 67% of deaths in the study occurred in subjects with diabetes.

The researchers examined the effects of diabetes treatments on adverse COVID-19 outcomes, focusing specifically on insulin and metformin as the 2 most common medications for type 2 diabetes. They found that prior insulin use did not have an impact on mortality risk.

Prior metformin use, however, significantly reduced the odds of dying. The 11% mortality for metformin users was not only comparable to that of the general COVID-19-positive population, but it was dramatically lower than the 23% mortality for patients with diabetes not on metformin. After controlling for other covariates, age, sex, and metformin use were independent factors affecting COVID-19-related mortality.

“Since similar results have now been obtained in different populations from around the world—including China, France, and a United Healthcare 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,” Shalev said.

Notably, even after controlling for covariates, the investigators found that death was significantly less likely for patients with type 2 diabetes taking metformin, compared with those not taking metformin. The researchers said future studies should explore how metformin is protective and should assess the risks and benefits of metformin treatment and indications for its use during the COVID-19 pandemic.

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

REFERENCE

Metformin use reduces risk of death for patients with COVID-19 and diabetes [news release]. University of Alabama at Birmingham; January 14, 2021. https://www.uab.edu/news/research/item/11795-metformin-use-reduces-risk-of-death-for-patients-with-covid-19-and-diabetes. Accessed January 19, 2021.