Diabetes, Drug Treatment and Mortality in COVID-19: A Multinational Retrospective Cohort Study

Abstract

Background: The risk of severe COVID-19 is potentiated by dysregulated inflammatory responses to the virus, and individuals with type 2 diabetes mellitus (T2DM) are particularly vulnerable. Glucose-regulating medications such as glucagon-like peptide-1 receptor (GLP-1R) agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, and pioglitazone are known to have anti-inflammatory effects. The goal of this study was to investigate whether treatment of T2DM with these drugs was associated with improved outcomes in patients with SARS-CoV-2 infection.Methods: In a multinational retrospective cohort study, we used the TriNetX COVID-19 Research Network of 50 large health care organizations to examine data from electronic medical records of 12,954 patients with T2DM who were diagnosed with COVID-19. We evaluated the relationship of the use of these drugs within 90 days preceding the diagnosis of COVID-19 with the incidence of hospital admissions, respiratory complications, and mortality within 28 days following the diagnosis of COVID-19.Findings: After matching for age, sex, race, ethnicity, body mass index, and comorbidities, results show significant reductions in hospital admissions of 54∙1%, 40∙0% and 20∙5%, and significant reductions in mortality of 68∙4%, 47∙0%, and 26∙3%, with use of pioglitazone, GLP-1R agonists, and DPP-4 inhibitors, respectively, within 90 days preceding the diagnosis of COVID-19. Respiratory complications also were reduced by 46∙0% and 24∙7% for patients treated with a GLP-1R agonist or pioglitazone, respectively. Finally, hospitalized patients who continued treatment with DPP-4 inhibitors had a 62∙8% relative decrease in the incidence of mortality when compared with those who discontinued treatment with DPP-4 inhibitors.Interpretation: In a multinational retrospective cohort study, use of GLP-1R agonists, pioglitazone, and DPP-4 inhibitors, is associated with reduced mortality and hospitalizations in patients with T2DM diagnosed with COVID-19. Randomized clinical trials are needed to further investigate this possibility.Funding: TriNetX network access supported by NCATS Award (TR002014). Merit Award from the National Institute on Drug Abuse DA009815 (PSG).Declaration of Interests: All authors declare no competing interests.Ethics Approval Statement: As a federated network, TriNetX has an IRB waiver as it only provides aggregated counts, statistical summaries of de-identified information, and no protected health information. Penn State College of Medicine has an agreement in place to access the TriNetX COVID-19 Research Network. All analyses were conducted using the browser-based real-time analytics feature of TriNetX.