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 1 s (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.