In a National Institutes of Health (NIH) supported observational study, the University of Alabama at Birmingham (UAB) revealed that patients with Type 2 diabetes on the drug metformin turned out to have a three-fold decrease in mortality due to COVID-19. These patients were using the diabetes drug prior to COVID-19 diagnosis. Led by Dr. Anath Shalev who directs UAB’s Comprehensive Diabetes Center, the study reveals that even when the study team adjusted for a number of variables (e.g. demographics or other health conditions), the beneficial correlation remained between metformin and reduction in COVID-19 death rate. As Dr. Shalev shared recently, similar findings have been discovered across populations in China, France and another UnitedHealthcare analysis. Could it be that these UAB findings are generalizable?
Could the Mechanism of Action Involve Anti-Inflammatory & Anti-Thrombotic Effects?
Recently elaborated by Jeff Hansen writing for the Alabama Newscenter, the study team doesn’t know what the mechanism of action is or how metformin actually betters a type 2 diabetes patient prognosis. They do suspect that the study results indicate that such mechanisms extend beyond the expected improvement glycemic control or obesity as Mr. Hansen reported that measurements, such as body mass index or blood glucose for that matter, became lower in the patients who ended up surviving versus those who passed away due to COVID-19. Dr. Shalev posited perhaps, “The mechanisms may involve metformin’s previously described anti-inflammatory and anti-thrombotic effects.”
Part of the a new Precision Diabetes Program—a collaboration between the UAB Comprehensive Diabetes Center and the Hugh Kaul Precision Medicine Institute at UAB—this study involved the analysis of 25,326 patients evaluated for COVID-19 at the tertiary care UAB Hospital between Feb. 25 and June 22, 2020. Out of the total patient population, 604 individuals were identified as COVID-19 positive and 311 of them were African Americans. The results of the study have been made available in MedRxiv and then peer-reviewed and published in Frontiers in Endocrinology. The ultimate endpoint under review for this study centered on mortality in COVID-19 positive patients as well as the association with patient demographics and comorbidities.
Racial disparities in health were on full display from this study. Blacks (African Americans) represent 26% of the state’s population and turned out to be 52% of those who tested positive for the coronavirus; only 30% of individuals tested negative were Black. Meanwhile, whites represented only 36% of the COVID-19-positive patients and 56% of the study population tested negative. The study team’s results revealed however that there was no material difference in mortality based on race for all those who were identified as COVID-19 positive.
Emphasizing this racial divide on infection rate, Dr. Shalev shared, “In our cohort being African American appeared to be primarily a risk factor for contracting COVID-19, rather than for mortality. This suggests that any racial disparity observed is likely due to exposure risk and external socioeconomic factors, including access to proper health care.”
Hansen writing for Alabama News Center reported that the overall mortality rate for the COVID-19 patients totaled 11%; 92% of the deaths involved patients aged over 50 and those who were male with higher blood pressure even higher risk. So was diabetes: 67% of the deaths involved patients with diabetes.
While the study team sought to better understand how diabetes treatments may worsen coronavirus outcomes, they looked at both insulin and metformin and determined that those that used insulin prior had no impact on mortality risk.
But the use of metformin prior to COVID-19 diagnosis had a real positive impact, that is negatively impacting death rates. At an 11% mortality rate for metformin users, this compared to the general COVID-19 positive patient base and importantly “…dramatically lower than the 23% mortality for diabetes patients not on metformin” writes Hansen.
Even after controlling for a number of covariates, a lower death rate in the metformin taking population “…suggests 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,” stated Dr. Shalev.
Anath Shalev, MD, professor in the UAB Department of Medicine Division of Endocrinology, Diabetes and Metabolism, holds the Nancy and Eugene Gwaltney Family Endowed Chair in Juvenile Diabetes and Metabolism, as well as the Nancy and Eugene Gwaltney Family Endowed Chair in Juvenile Diabetes Research.
Andrew Crouse, PhD, Director Research Operations, Hugh Kaul Precision Medicine Institute, UAB
Matthew Might, Director, Hugh Kaul Precision Medicine Institute, UAB
Tiffany Grimes, Hugh Kaul Precision Medicine Institute, UAB
Fernando Ovalle, MD, Hugh Kaul Precision Medicine Institute, UAB
Peng Li, PhD, Assistant Professor, UAB School of Nursing
Call to Action: The researchers believe more research is necessary to better understand how this cheap generic drug used for diabetes is protective as well as evaluate the risks and benefits of possible use of the drug in this ongoing pandemic.