open access publication

Article, 2024

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

Diabetes Therapy, ISSN 1869-6953, 1869-6961, Volume 15, 5, Pages 1169-1186, 10.1007/s13300-024-01562-1

Contributors

Klein, Klara Rachel 0000-0002-5894-9054 (Corresponding author) [1] Abrahamsen, Trine Julie [2] Kahkoska, Anna Rachel 0000-0003-2701-101X [1] Alexander, George Caleb [3] [4] Chute, Christopher G 0000-0001-5437-2545 [3] Haendel, Melissa Anne 0000-0001-9114-8737 [5] Hong, Stephanie S 0000-0002-0795-1293 [3] [4] Mehta, Hemalkumar B [3] Moffitt, Richard Austin 0000-0003-2723-5902 [6] Stürmer, Til [1] Kvist, Kajsa [2] Buse, John Bernard 0000-0002-9723-3876 [1]

Affiliations

  1. [1] University of North Carolina at Chapel Hill
    2. [NORA names: United States; America, North; OECD];
  2. [2] Novo Nordisk (Denmark)
    3. [NORA names: Novo Nordisk; Private Research; Denmark; Europe, EU; Nordic; OECD];
  3. [3] Johns Hopkins University
    4. [NORA names: United States; America, North; OECD];
  4. [4] Johns Hopkins Medicine
    5. [NORA names: United States; America, North; OECD];
  5. [5] University of Colorado Anschutz Medical Campus
    6. [NORA names: United States; America, North; OECD];

Abstract

IntroductionPeople 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.MethodsUtilizing 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).ResultsUse 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.ConclusionAmong 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.Graphical Abstract

Keywords

Abstract, COVID-19, COVID-19 infection, COVID-19 outcomes, COVID-19 severity, Cohort Collaboration, ConclusionAmong adults, DPP-4i, DPP-4i use, ER visits, GLP-1RA, GLP1-RA, Graphical abstract, National, National COVID Cohort Collaborative, PCR test, ResultsUsing, SARS-CoV-2, SARS-CoV-2 PCR test, SGLT-2i use, Secondary outcomes, acute respiratory syndrome coronavirus 2, admission, adults, agonists, article, associated with lower odds, association, baseline, baseline characteristics, characteristics, collaboration, combination, concomitant use, coronavirus 2, cotransporter-2 inhibitors, data, date, days, emergency, emergency room, estimation, glucagon-like peptide-1 receptor agonists, heightened risk, hospital, impact, individuals, infection, inhibitors, intensive care unit admission, likelihood estimation, lower odds, maximum likelihood estimation, mechanical ventilation, monotherapy, months, mortality, observational data, odds, odds ratio, outcomes, peptide-1 receptor agonists, positive SARS-CoV-2 PCR test, positive test date, premorbid use, prescription, primary outcome, ratio, receptor agonists, respiratory syndrome coronavirus 2, risk, room, severe acute respiratory syndrome coronavirus 2, severity, severity of outcome, sodium-glucose cotransporter-2 inhibitor use, sodium-glucose cotransporter-2 inhibitors, study, syndrome coronavirus 2, targeted maximum likelihood estimation, test, test date, therapy, type, type 2 diabetes, unit admission, use, ventilation, visits

Funders

  • National Institute of Diabetes and Digestive and Kidney Diseases
  • National Center for Advancing Translational Sciences
  • American Diabetes Association
  • Novo Nordisk (Denmark)
  • National Institute on Aging
  • National Institute on Minority Health and Health Disparities
  • National Heart Lung and Blood Institute

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