Diabetes is one of the comorbidities most strongly associated with severe coronavirus disease 2019 (COVID-19) in the United States, and data from early in the pandemic suggested individuals with type 2 diabetes faced twice the risk of death from COVID-19, as well as a greater risk of requiring hospitalization and intensive care.
The National COVID Collaborative (N3C), a partnership of NIH Clinical and Science Award Program hubs, conducted a study of data from 12,446 individuals with type 2 diabetes who had fallen severely ill with COVID-19 in 2020. These scientists found that individuals who had been treated with certain kinds of diabetes medications fared better than those who were treated with a different type of medication.
This research was published in Diabetes Cares, the journal of the American Diabetes Association.
Two classes of medications that lower blood sugar - glucagon-like peptide 1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) - have been associated with a reduction of cardiorenal events and mortality in previous large trials of cardiovascular outcomes, heart failure, and renal outcomes, in populations at high risk of cardiorenal events. Benefits associated with these medications appear most pronounced among individuals with type 2 diabetes and comorbid cardiovascular disease, heart failure, chronic kidney disease, and obesity, conditions that also incur the highest risk for severe COVID-19.
Additionally, scientists have speculated about plausible mechanisms for the protective effects of GLP1-RA and SGLT2i in COVID-19, independent of their glycemic effects. Yet, it is not known how the use of new medications is associated with severity of COVID-19.
"Our objective was to characterize the association of premorbid use of GLP1-RA and SGLT2i with COVID-19 outcomes," said senior author John Buse, MD, PhD, director of the NC Translational and Clinical Sciences (NC TraCS) Institute and the UNC Diabetes Care Center. "The study hypothesis was that use of both classes of medications would be associated with improved outcomes in the setting of COVID-19 infection. And characterizing these associations could reveal treatment strategies to improve outcomes for a population at high risk for COVID-19-associated mortality."
For the study, the researchers selected individuals using dipeptidyl peptidase 4 inhibitors (DPP4i) as a comparator group to individuals taking GLP1-RA or SGLT2i medications because DPP4i medications can also be considered for second-line use after the initiation of metformin and have been used in other real-world analyses.
To determine the respective associations of premorbid glucagon-like peptide-1 receptor agonist (GLP1-RA) and sodium-glucose cotransporter 2 inhibitor (SGLT2i) use, compared with premorbid dipeptidyl peptidase 4 inhibitor (DPP4i) use, with severity of outcomes in the setting of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
Of the 12,446 individuals, the 60-day mortality was 3.11%, with 2.06% for GLP1-RA use, 2.32% for SGLT2i use, and 5.67% for DPP4i use. Both GLP1-RA and SGLT2i use were associated with lower 60-day mortality compared with DPP4i use. Use of both GLP1-RA and SGLT2i medications was also associated with decreased total mortality, emergency room visits, and hospitalizations, though the individuals taking DPP4i medications were older and generally sicker.
N3C is a COVID research platform funded by the National Institute of Health's National Center for Advancing Translational Sciences including data on over 2 million people with a positive COVID test. The UNC Translational and Clinical Sciences (TraCS) Institute helped develop N3C and supports efforts to use the data to develop better treatment and prevention programs for COVID.
Other authors of the Diabetes Care paper are first author Anna Kahkoska, Trine Julie Abrahamsen, G. Caleb Alexander, Tellen D. Bennett, Christopher G. Chute, Melissa A. Haendel, Klara R. Klein, Hemalkumar Mehta, Joshua D. Miller, Richard A. Moffitt, Til Stürmer, and Kajsa Kvist.
John Buse is the Verne S. Caveness Distinguished Professor of Medicine and endocrinology division chief at the UNC School of Medicine. Kahkoska is an assistant professor in the UNC Department of Nutrition at the UNC Gillings School of Global Public Health and the UNC School of Medicine.
