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

42 Pages Posted: 30 Nov 2020

See all articles by Jennifer E. Nyland

Jennifer E. Nyland

Pennsylvania State University - Penn State College of Medicine

Nazia T. Raja-Khan

Pennsylvania State University - Department of Neural and Behavioral Sciences

Kerstin Bettermann

Pennsylvania State University - Department of Neural and Behavioral Sciences

Philippe A. Haouzi

Pennsylvania State University - Department of Neural and Behavioral Sciences

Jennifer L. Kraschnewski

Pennsylvania State University - Department of Neural and Behavioral Sciences

Leslie J. Parent

Pennsylvania State University - Department of Neural and Behavioral Sciences

Patricia Sue Grigson

Pennsylvania State University - Department of Neural and Behavioral Sciences

More...

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.

Keywords: COVID-19, SARS-CoV-19, Diabetes

Suggested Citation

Nyland, Jennifer E. and Raja-Khan, Nazia T. and Bettermann, Kerstin and Haouzi, Philippe A. and Kraschnewski, Jennifer L. and Parent, Leslie J. and Grigson, Patricia Sue, Diabetes, Drug Treatment and Mortality in COVID-19: A Multinational Retrospective Cohort Study. Available at SSRN: https://ssrn.com/abstract=3725612 or http://dx.doi.org/10.2139/ssrn.3725612

Jennifer E. Nyland

Pennsylvania State University - Penn State College of Medicine

700 HMC Crescent Road Hershey
Hershey, PA 17033
United States

Nazia T. Raja-Khan

Pennsylvania State University - Department of Neural and Behavioral Sciences ( email )

Kerstin Bettermann

Pennsylvania State University - Department of Neural and Behavioral Sciences ( email )

Philippe A. Haouzi

Pennsylvania State University - Department of Neural and Behavioral Sciences ( email )

Jennifer L. Kraschnewski

Pennsylvania State University - Department of Neural and Behavioral Sciences ( email )

Leslie J. Parent

Pennsylvania State University - Department of Neural and Behavioral Sciences ( email )

Patricia Sue Grigson (Contact Author)

Pennsylvania State University - Department of Neural and Behavioral Sciences ( email )

Hershey, PA
United States

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