C108-02 Changes in Respiratory Physiology Following Initiation of GLP-1 Receptor Agonists (GLP-1RA)

Rationale Obesity and insulin resistance promote metabolic and inflammatory dysregulation, impairing lung function through mechanical stress and immune-mediated inflammation. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) demonstrate preclinical benefits in reducing airway inflammation and hyperresponsiveness by lowering epithelial cytokines. Studies suggest GLP-1RA use is associated with fewer asthma/Chronic Obstructive Pulmonary Disease(COPD) exacerbations among populations with obesity and diabetes. Traditional spirometry may be insensitive to early airway changes; thus, we profiled pulmonary function using multiple modalities among patients newly initiated on GLP-1RAs. Methods This is a prospective, single-center cohort study at the Providence VA Medical Center. Participants newly prescribed a GLP-1RA were identified through endocrinology and pharmacy clinics. Baseline assessments, including fractional exhaled nitric oxide(FeNO), IOS, spirometry, and the Chronic Respiratory Disease Questionnaire(CRQ), were performed before GLP-1RA initiation and at 12-14 weeks. This pilot evaluated the feasibility of recruitment, repeat testing, and changes in pulmonary function and CRQ scores. Baseline and follow-up data were compared using paired t-tests or Wilcoxon signed-rank tests, as appropriate. To date, 13 participants have been enrolled, with 7 completing both assessments. Results All participants were male, with a mean age of 57.1 years, and lost an average of 10 kg during the study. Results are summarized in Table 1. Among those completing follow-up, 43% (n = 3/7) achieved a reduction of more than 20% in FeNO. Oscillometry parameters showed uniform directional improvement: R5(total airway resistance) and R5-R20(small-airway resistance) decreased, accompanied by less negative X5(reactance) values, a downward trend in AX, and a decline in Fres(resonant frequency). Spirometry demonstrated directional improvement in FEV1/FVC, ΔFEV1, ΔFVC, and FEF25-75. The mean FEV1 improvement was 160cc. CRQ scores improved across all domains, with significant changes in Fatigue, Mastery, and total scores. Conclusion GLP-1RA therapy was associated with clinically meaningful improvements in FeNO and FEV1, and potentially meaningful improvements in small-airway function, as measured by oscillometry, although not statistically significant. Patient-reported respiratory outcomes improved significantly. These changes may be partly attributable to GLP-1RA use rather than weight loss, as participants showed modest reductions in body weight, below the 10% threshold linked to physiologic benefit. Impulse oscillometry served as a sensitive, noninvasive tool for detecting early small-airway changes. This study contributes to the existing literature by highlighting small-airway disease and utilizing oscillometry to evaluate early changes in lung function in patients treated with GLP-1RA. The dataset will mature with continued recruitment, and continued testing will strengthen these findings.