US Pharm. 2021;46(2):3.

Patients with type 2 diabetes who were using metformin prior to a diagnosis of COVID-19 were associated with a threefold decrease in mortality, according to a racially diverse study at the University of Alabama at Birmingham (UAB). Diabetes is a significant comorbidity for COVID-19. Even after correcting for age, sex, race, obesity, and hypertension or chronic kidney disease and heart failure, according to Anath Shalev, MD, study leader and director of UAB’s Comprehensive Diabetes Center, the beneficial effect remained.

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

How metformin improves prognosis among COVID-19 patients is unknown, according to Dr. Shalev. The UAB research results suggest that the explanation may extend beyond improvement in glycemic control or obesity, since neither BMI, blood glucose, nor hemoglobin A1C were lower in the metformin users who survived compared with those who died.

Instead, she suggests, anti-inflammatory effects might hold the key. “The mechanisms may involve metformin’s previously described anti-inflammatory and antithrombotic effects.”

The study analyzing mortality in COVID-19–positive subjects—first published in MedRxiv and subsequently in Frontiers in Endocrinology—included 25,326 patients tested for COVID-19 at the tertiary-care UAB Hospital between February 25 and June 22, 2020. Of the 604 patients testing COVID-19–positive, 311 were African American.

Overall mortality for COVID-19–positive patients was 11%. The study found that 93% of deaths occurred in subjects older than age 50 years, and 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. Overall, 67% of deaths in the study occurred in subjects with diabetes.

The researchers looked at the effects of diabetes treatment on adverse COVID-19 outcomes, focusing on insulin and metformin as the two most common medications for type 2 diabetes. They discovered that prior insulin use did not affect mortality risk. However, prior metformin use was another story. Metformin use significantly reduced the odds of death from COVID-19, and the 11% mortality for metformin users was not only comparable to that of the general COVID-19–positive population, but also significantly lower than the mortality for diabetes patients not taking metformin—23%.

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