New research suggests that the use of the diabetes drug metformin prior to a 2019 coronavirus disease (COVID-19) diagnosis was linked to a decrease in mortality in patients with type 2 diabetes.
Diabetes is a significant comorbidity for COVID-19, and while researchers still don’t know how metformin improves the prognosis for COVID-19, the study results suggest that the mechanisms may go beyond any expected improvements in glycemic control of obesity. The researchers found that neither the body mass index, blood sugar nor A1C hemoglobin were lower in the surviving metformin users than in the deceased.
“The mechanisms may include metformin’s previously described anti-inflammatory and antithrombotic effects,” said Dr. Anath Shalev, head of the study, in a press release.
The study included 25,326 patients tested for COVID-19 between February 25 and June 22, 2020 at the University of Alabama tertiary care at Birmingham Hospital. Of the 604 patients who tested positive, 311 were black. The primary outcome was mortality in COVID-19 positive patients, and the researchers examined the possible association with subject characteristics or comorbidities.
Investigators found that African Americans, who make up just 26% of Alabama’s population, made up 52% of those who tested positive for COVID-19 and only 30% of those who tested negative. In contrast, 36% of the COVID-19 positive subjects were white, while whites made up 56% of the subjects who tested negative. Although these results reveal significant racial diversity, the researchers found that no significant racial differential in mortality was observed after the diagnosis of COVID-19.
“In our cohort, African American appeared to be primarily a risk factor for contracting COVID-19, rather than mortality,” Shalev said in a press release. “This suggests that any observed racial differences are likely due to exposure risk and external socio-economic factors, including access to adequate health care.”
The overall mortality for patients with COVID-19 was 11%, and the researchers found that 93% of deaths occurred in patients over the age of 50, while men or high blood pressure were associated with a significantly increased risk of death. Diabetes was associated with a dramatic increase in mortality, with an odds ratio of 3.62. Notably, 67% of the deaths in the study occurred in patients with diabetes.
Researchers looked at the effects of diabetes treatments on unwanted COVID-19 outcomes, specifically focusing on insulin and metformin as the two most common drugs for type 2 diabetes. They found that previous insulin use had no effect on mortality risk.
However, previous use of metformin significantly reduced the likelihood of death. The 11% mortality for metformin users was not only comparable to that of the general COVID-19 positive population, but also dramatically lower than the 23% mortality for patients with diabetes who did not receive metformin. When other covariates were controlled, age, gender, and metformin use were independent factors influencing COVID-19-related mortality.
“With similar results now being seen in different populations around the world – including China, France and an analysis by United Healthcare – this suggests the observed reduction in mortality risk associated with metformin use in patients with type 2 diabetes and COVID-19 might be generalizable, ”Shalev said.
Specifically, after checking the covariates, the researchers found that death in patients with type 2 diabetes who took metformin was significantly less than in patients who did not take metformin. The researchers said future studies should investigate how metformin protects and assess the risks and benefits of treatment with metformin, as well as the 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, that risk is dramatically reduced in patients taking metformin. This increases the possibility that metformin will offer a protective approach in this high-risk population.” so Shalev concluded.
The use of metformin reduces the risk of death in 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.