Association Between Glucagon-Like Peptide 1 Receptor Agonist and Sodium-Glucose Cotransporter 2 Inhibitor Use and COVID-19 Outcomes

UMMS Affiliation

UMass Center for Clinical and Translational Science

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Document Type



Amino Acids, Peptides, and Proteins | Endocrinology, Diabetes, and Metabolism | Epidemiology | Hormones, Hormone Substitutes, and Hormone Antagonists | Infectious Disease | Translational Medical Research | Virus Diseases


OBJECTIVE: 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.

RESEARCH DESIGN AND METHODS: We analyzed observational data from SARS-CoV-2-positive adults in the National COVID Cohort Collaborative (N3C), a multicenter, longitudinal U.S. cohort (January 2018-February 2021), with a prescription for GLP1-RA, SGLT2i, or DPP4i within 24 months of positive SARS-CoV-2 PCR test. The primary outcome was 60-day mortality, measured from positive SARS-CoV-2 test date. Secondary outcomes were total mortality during the observation period and emergency room visits, hospitalization, and mechanical ventilation within 14 days. Associations were quantified with odds ratios (ORs) estimated with targeted maximum likelihood estimation using a super learner approach, accounting for baseline characteristics.

RESULTS: The study included 12,446 individuals (53.4% female, 62.5% White, mean +/- SD age 58.6 +/- 13.1 years). The 60-day mortality was 3.11% (387 of 12,446), with 2.06% (138 of 6,692) for GLP1-RA use, 2.32% (85 of 3,665) for SGLT2i use, and 5.67% (199 of 3,511) for DPP4i use. Both GLP1-RA and SGLT2i use were associated with lower 60-day mortality compared with DPP4i use (OR 0.54 [95% CI 0.37-0.80] and 0.66 [0.50-0.86], respectively). Use of both medications was also associated with decreased total mortality, emergency room visits, and hospitalizations.

CONCLUSIONS: Among SARS-CoV-2-positive adults, premorbid GLP1-RA and SGLT2i use, compared with DPP4i use, was associated with lower odds of mortality and other adverse outcomes, although DPP4i users were older and generally sicker.


diabetes, comorbidities, COVID-19, UMCCTS funding

DOI of Published Version



Kahkoska AR, Abrahamsen TJ, Alexander GC, Bennett TD, Chute CG, Haendel MA, Klein KR, Mehta H, Miller JD, Moffitt RA, Stürmer T, Kvist K, Buse JB; N3C Consortium. Association Between Glucagon-Like Peptide 1 Receptor Agonist and Sodium-Glucose Cotransporter 2 Inhibitor Use and COVID-19 Outcomes. Diabetes Care. 2021 Jul;44(7):1564-1572. doi: 10.2337/dc21-0065. Epub 2021 Jun 16. PMID: 34135013; PMCID: PMC8323175. Link to article on publisher's site

Journal/Book/Conference Title

Diabetes care


The UMass Center for Clinical and Translational Science (UMCCTS), UL1TR001453, helped fund this study.

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