Pulmonary response to glucagon-like peptide-1 receptor agonist therapy in adults with cystic fibrosis-related diabetes: factors associated with improvement in FEV1.

BACKGROUND: Obesity and cardiometabolic dysfunction are increasingly recognized among people with cystic fibrosis (pwCF) in the CFTR modulator era. Emerging evidence suggests glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may influence pulmonary physiology and respiratory outcomes in pwCF. However, factors associated with pulmonary response remain poorly understood. We hypothesized that pulmonary improvement following GLP-1 RA initiation would be associated with both metabolic response and treatment intensity. METHODS: We performed a retrospective cohort study of adults with CF-related diabetes (CFRD) treated with GLP-1 RAs. Clinical, metabolic, and pulmonary variables were assessed following GLP-1 RA initiation. Associations between baseline characteristics, treatment-related factors, and change in forced expiratory volume in one second (FEV1) were evaluated using regression analyses. RESULTS: Twenty-three adults with CFRD treated with GLP-1 RAs were included. Median FEV1 increased by 6.0 percentage points (IQR 3.5-10.0) over 6 months following therapy initiation. Greater reduction in body mass index (BMI) and achievement of therapeutic GLP-1 RA dosing were both associated with greater improvement in FEV1. Importantly, the association between therapeutic-dose GLP-1 RA therapy and improved FEV1 persisted after adjustment for BMI reduction, suggesting that pulmonary improvement may not be fully explained by weight loss alone. CONCLUSIONS: In adults with CFRD, greater BMI reduction and achievement of therapeutic GLP-1 RA dosing were associated with greater improvement in FEV1. These findings support further investigation of GLP-1 RAs as a potential therapeutic strategy that may influence pulmonary outcomes while improving metabolic health in pwCF.