The Potential Impact of GLP-1 Receptor Agonists on Exacerbation Risk in Patients with COPD and Type 2 Diabetes: A Real-World Population-Based Observational Study

Bernardino Alcázar-Navarrete,1 Heath Heatley,2 Alan Kaplan,3 Lee Tze Tan,4 Mariko Siyue Koh,5 Naveed Sattar,6 John Townend,2 Derek Skinner,2 Victoria Carter,2 David Price2 1Professor at Department of Medicine. Respiratory Department. Hospital Universitario Virgen de Las Nieves. Ibs, Granada, University of Granada, Granada, Spain; 2Observational and Pragmatic Research Institute, Singapore, Singapore; 3Family Physician Airways Group of Canada, Stouffville, Ontario, Canada; 4National University Health System, Department of Family Medicine, Singapore, Singapore; 5Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore, Singapore; 6Professor of Cardiometabolic Medicine at the School of Cardiovascular & Metabolic Health at the University of Glasgow, Glasgow, UKCorrespondence: David Price, Observational and Pragmatic Research Institute, 22 Sin Ming Lane, #06-76, Midview City, Singapore, Singapore, 573969, Tel +65 3105 1489, Email [email protected]: There is limited evidence on the impact of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with chronic obstructive pulmonary disease (COPD).Material and Methods: We conducted a retrospective matched cohort study including patients aged ≥ 40 years with COPD and T2D. Patients initiating GLP-1 RAs were matched 1:1 with GLP-1 naïve controls based on age, sex, smoking status, COPD treatment (LABA/LAMA/ICS), and exacerbation history. The index date was defined as the first GLP-1 RA prescription, control’s index date was a COPD consultation within 186 days of matched patient index. The primary outcome was the number of COPD exacerbations during the 12 months following the index date. Secondary outcomes included oral corticosteroid (OCS) prescriptions and hospital resource utilization (HCRU). Poisson regression models adjusted for BMI and other confounders were used to estimate incidence rate ratios (IRR).Results: A total of 4479 matched patients were included. There were no significant differences between groups in exacerbation rates or OCS use in the year prior to the index date. During follow-up, patients treated with GLP-1 RAs had significantly fewer exacerbations (adjusted IRR [aIRR] 0.84, 95% CI: 0.79– 0.89) and fewer OCS prescriptions (aIRR 0.86, 95% CI: 0.77– 0.95) compared with controls. A significant delay in time to first OCS prescription was also observed.Conclusion: In this real-world cohort, initiation of GLP-1 RA treatment in patients with COPD and T2D was associated with lower COPD exacerbations and OCS use. These findings suggest a potential role for GLP-1 RAs in modifying the course of COPD in this comorbid population, warranting randomised trials.Keywords: COPD, obesity, COPD outcomes, GLP-1 RA