MON-535 Glucagon-Like-Peptide-1 Receptor Agonists Are Effective in Patients with Cystic Fibrosis

Abstract Disclosure: E. Mignone: None. L.A. Ephraums: None. A. Routley: None. M. Judith: None. H. Emily: None. S. Chapman: None. L. Gagliardi: None. U. Mahesh: None. Background: Cystic fibrosis related diabetes (CFRD), prevalent in up to 50% of adults with cystic fibrosis (CF) has traditionally been managed with insulin monotherapy due to the predominant aetiology being insulin deficiency. Insulin monotherapy has been standard of care as per the Clinical Care Guidelines published by the Diabetes Association. Obesity rates are rapidly increasing in CF patients due to the introduction of highly efficacious cystic fibrosis transmembrane regulator (CFTR) modulator therapies. In addition, a reduced incretin response in glycaemic control has been demonstrated in CFRD and contributes to dysglycaemia, raising the question regarding glucagon-like polypeptide-1 receptor agonist (GLP-1RA) efficacy. Aim: Assess the efficacy of GLP-1RA use in CF and CFRD. Methods: A retrospective analysis of the Royal Adelaide Hospital Cystic Fibrosis Clinic was performed. 11 individuals with cystic fibrosis had utilised a GLP-1RA, 8 had diabetes and 3 individuals did not have diabetes. All used GLP-1RA for at least 6 months, with the median duration of therapy being 9 months. The median semaglutide dose was 0.5mg (0.125-1mg) weekly. Results: Median forced expiratory volume (FEV1) improved by 5.5% (IQR -0.5 - 11.25, p=0.02) post initiation of GLP-1RA including those with and without diabetes. FEV1 increased by a median of 190ml post initiation of GLP-1RA (p=0.0093). The median forced vital capacity (FVC) increase was only 8ml (p=0.06). Median Hba1c reduced by 1.5% (-0.68 - -2.58, p=0.016). The median time spent in range (BGL 3.9-10.0mmol/L) increased by 21% (18 - 48, p=0.016). There were no significant difference in total daily insulin dose, however this was confounded by an outlier. If this individual was removed the results were highly significant with median reduction of 11 units per day (p=0.016). The median weight reduction were 4.25 kg (-8.0 - -1.4, p=0.002). The mean change in BMI were -1.37 kg/m2 (-2.4 - -0.5). No patients BMI reduced below the healthy BMI range. Conclusion: This data provides significant contribution to the only small body of evidence present for the efficacy of GLP-1RA in CF and CFRD. GLP-1RA improves HbA1c, time in range and reduces total insulin daily dose. Specific to a CF population, there is an improved FEV1 which is independent of any clinically significant change in FVC. Whilst this may be related to improved glycaemic control, this phenomenon is also seen in the CF group without diabetes. Weight loss is also achievable, while maintaining a healthy BMI range. Although current guidelines suggest insulin monotherapy, GLP-1RA should be considered in the management of CFRD as well as CF related obesity given our experience. Presentation: Monday, July 14, 2025