Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2026
Changes in metabolic and pulmonary outcomes after discontinuation of glucagon-like-peptide-1 receptor agonist therapy in people with cystic fibrosis.
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Singh Akruti, Horvit Andrew, Abramowitz Jessica, Abreu Marconi, Kaput Katie, Neece Amber, Ratti Gregory A, Finklea James D, Jain Raksha, Mirfakhraee Sasan
Аннотация
BACKGROUND: GLP-1 receptor agonists (GLP-1 RAs) are being increasingly prescribed off-label to people with cystic fibrosis (pwCF) for weight management or cystic fibrosis-related diabetes (CFRD). However, the metabolic and pulmonary consequences of GLP-1 RA discontinuation in pwCF are unknown. We evaluated changes in body mass index (BMI), glucose control, pulmonary function, and pulmonary exacerbations following GLP-1 RA withdrawal.
METHODS: We conducted a single-arm, retrospective, multi-center cohort study of adults with CF treated with GLP-1 RAs who subsequently discontinued treatment for ≥ 6 months to assess the effect on metabolic and pulmonary outcomes. BMI, hemoglobin A1c (HbA1c), percent predicted forced expiratory volume in 1 second (FEV1), and forced vital capacity (FVC) were collected prior to GLP-1 RA, during GLP-1 RA therapy, and 6 months post-GLP-1 RA discontinuation.
RESULTS: Fourteen pwCF (four male; median age 45 years) met inclusion criteria. Median BMI at GLP-1 RA initiation was 34.3 kg/m². BMI decreased by a median of 10.8% during GLP-1 RA therapy, followed by a median increase of 5.6% in the six months after GLP-1 RA discontinuation. Median FEV1 increased from 64.5% at baseline to 76.5% on therapy and remained stable at 73.0% six months after GLP-1 RA discontinuation; similar patterns were observed for FVC. Annualized FEV1 slopes were -0.9% pre-treatment, +1.3% during treatment, and +0.9% post discontinuation. HbA1c improved with GLP-1 RA therapy and remained stable after withdrawal. Pulmonary exacerbations remained infrequent in all periods.
CONCLUSIONS: In pwCF, GLP-1 RA discontinuation is followed by partial weight regain but with stable pulmonary and glycemic outcomes. Larger, prospective studies are needed to confirm these preliminary findings and guide clinical decision-making regarding GLP-1 RA use in this population.
METHODS: We conducted a single-arm, retrospective, multi-center cohort study of adults with CF treated with GLP-1 RAs who subsequently discontinued treatment for ≥ 6 months to assess the effect on metabolic and pulmonary outcomes. BMI, hemoglobin A1c (HbA1c), percent predicted forced expiratory volume in 1 second (FEV1), and forced vital capacity (FVC) were collected prior to GLP-1 RA, during GLP-1 RA therapy, and 6 months post-GLP-1 RA discontinuation.
RESULTS: Fourteen pwCF (four male; median age 45 years) met inclusion criteria. Median BMI at GLP-1 RA initiation was 34.3 kg/m². BMI decreased by a median of 10.8% during GLP-1 RA therapy, followed by a median increase of 5.6% in the six months after GLP-1 RA discontinuation. Median FEV1 increased from 64.5% at baseline to 76.5% on therapy and remained stable at 73.0% six months after GLP-1 RA discontinuation; similar patterns were observed for FVC. Annualized FEV1 slopes were -0.9% pre-treatment, +1.3% during treatment, and +0.9% post discontinuation. HbA1c improved with GLP-1 RA therapy and remained stable after withdrawal. Pulmonary exacerbations remained infrequent in all periods.
CONCLUSIONS: In pwCF, GLP-1 RA discontinuation is followed by partial weight regain but with stable pulmonary and glycemic outcomes. Larger, prospective studies are needed to confirm these preliminary findings and guide clinical decision-making regarding GLP-1 RA use in this population.