Association of Premorbid GLP-1RA and SGLT-2i Prescription Alone and in Combination with COVID-19 Severity

Klara R Klein; Trine J Abrahamsen; Anna R Kahkoska; G Caleb Alexander; Christopher G Chute; Melissa Haendel; Stephanie S Hong; Hemalkumar Mehta; Richard Moffitt; Til Stürmer; Kajsa Kvist; John B Buse; N3C Consortium

doi:10.1007/s13300-024-01562-1

Association of Premorbid GLP-1RA and SGLT-2i Prescription Alone and in Combination with COVID-19 Severity

Diabetes Ther. 2024 May;15(5):1169-1186. doi: 10.1007/s13300-024-01562-1. Epub 2024 Mar 27.

Authors

Klara R Klein¹, Trine J Abrahamsen², Anna R Kahkoska^{3

4}, G Caleb Alexander^{5

6

7}, Christopher G Chute⁸, Melissa Haendel⁹, Stephanie S Hong⁷, Hemalkumar Mehta⁶, Richard Moffitt¹⁰, Til Stürmer¹¹, Kajsa Kvist², John B Buse³; N3C Consortium

Affiliations

¹ Division of Endocrinology and Metabolism, Department of Medicine, University of North Carolina School of Medicine, Campus Box #7172, 8072 Burnett Womack, 160 Dental Circle, Chapel Hill, NC, 27599, USA. klara_klein@med.unc.edu.
² Novo Nordisk A/S, Søborg, Denmark.
³ Division of Endocrinology and Metabolism, Department of Medicine, University of North Carolina School of Medicine, Campus Box #7172, 8072 Burnett Womack, 160 Dental Circle, Chapel Hill, NC, 27599, USA.
⁴ Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, USA.
⁵ Center for Drug Safety and Effectiveness, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
⁶ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
⁷ Division of General Internal Medicine, Johns Hopkins Medicine, Johns Hopkins University, Baltimore, MD, USA.
⁸ Schools of Medicine, Public Health, and Nursing, Johns Hopkins University, Baltimore, MD, 21287, USA.
⁹ Center for Health AI, University of Colorado School of Medicine, Aurora, CO, USA.
¹⁰ Department of Biomedical Informatics, Stony Brook University, Stony Brook, NY, USA.
¹¹ Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Abstract

Introduction: People with type 2 diabetes are at heightened risk for severe outcomes related to COVID-19 infection, including hospitalization, intensive care unit admission, and mortality. This study was designed to examine the impact of premorbid use of glucagon-like peptide-1 receptor agonist (GLP-1RA) monotherapy, sodium-glucose cotransporter-2 inhibitor (SGLT-2i) monotherapy, and concomitant GLP1-RA/SGLT-2i therapy on the severity of outcomes in individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Methods: Utilizing observational data from the National COVID Cohort Collaborative through September 2022, we compared outcomes in 78,806 individuals with a prescription of GLP-1RA and SGLT-2i versus a prescription of dipeptidyl peptidase 4 inhibitors (DPP-4i) within 24 months of a positive SARS-CoV-2 PCR test. We also compared concomitant GLP-1RA/SGLT-2i therapy to GLP-1RA and SGLT-2i monotherapy. The primary outcome was 60-day mortality, measured from the positive test date. Secondary outcomes included emergency room (ER) visits, hospitalization, and mechanical ventilation within 14 days. Using a super learner approach and accounting for baseline characteristics, associations were quantified with odds ratios (OR) estimated with targeted maximum likelihood estimation (TMLE).

Results: Use of GLP-1RA (OR 0.64, 95% confidence interval [CI] 0.56-0.72) and SGLT-2i (OR 0.62, 95% CI 0.57-0.68) were associated with lower odds of 60-day mortality compared to DPP-4i use. Additionally, the OR of ER visits and hospitalizations were similarly reduced with GLP1-RA and SGLT-2i use. Concomitant GLP-1RA/SGLT-2i use showed similar odds of 60-day mortality when compared to GLP-1RA or SGLT-2i use alone (OR 0.92, 95% CI 0.81-1.05 and OR 0.88, 95% CI 0.76-1.01, respectively). However, lower OR of all secondary outcomes were associated with concomitant GLP-1RA/SGLT-2i use when compared to SGLT-2i use alone.

Conclusion: Among adults who tested positive for SARS-CoV-2, premorbid use of either GLP-1RA or SGLT-2i is associated with lower odds of mortality compared to DPP-4i. Furthermore, concomitant use of GLP-1RA and SGLT-2i is linked to lower odds of other severe COVID-19 outcomes, including ER visits, hospitalizations, and mechanical ventilation, compared to SGLT-2i use alone. Graphical abstract available for this article.

Keywords: COVID-19; GLP-1RA; National COVID Cohort Collaborative (N3C); Observational data; SARS-CoV-2; SGLT-2i; Type 2 diabetes.

Abstract

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