A72-12 Semaglutide and Cystic Fibrosis: Recognizing GI Interactions in Complex Physiology

Abstract Introduction Glucagon-like peptide-1 (GLP-1) receptor agonists, such as semaglutide, are widely used for diabetes and obesity due to their effects on glycemic control and weight loss. However, they frequently cause gastrointestinal (GI) side effects including nausea, delayed gastric emptying, and constipation. In cystic fibrosis (CF), baseline GI dysfunction from pancreatic insufficiency, altered motility, and stool burden may heighten these risks. Despite increasing use, data on GLP-1 agonists in CF are limited. We present a case illustrating significant GI intolerance to semaglutide in CF, emphasizing the importance of recognizing drug-disease interactions. Case Description A 27-year-old woman with cystic fibrosis and pancreatic insufficiency presented with worsening constipation, bloating, and abdominal pain three months after starting semaglutide 0.5 mg weekly for weight management. She developed early satiety and intermittent nausea soon after initiation and never escalated the dose. Despite dietary changes, hydration, and polyethylene glycol up to four times daily, she remained unable to pass stool for up to a week. On presentation, vital signs were normal and abdominal exam showed mild distension without peritoneal signs. Laboratory studies revealed normal electrolytes and a white blood cell count of 5.4 × 109/L. CT abdomen and pelvis demonstrated no obstruction but showed a dilated appendix without inflammation and significant stool burden, consistent with medication-induced dysmotility rather than appendicitis. She discontinued semaglutide and received an enema with prompt relief. At three-month follow-up, she reported complete resolution of symptoms without recurrence. Discussion This case underscores the need for vigilance when prescribing GLP-1 receptor agonists in patients with CF, as underlying motility disturbances and pancreatic insufficiency may amplify drug-induced GI adverse effects. The delayed gastric emptying and reduced intestinal transit associated with semaglutide can interact with CF-related dysmotility to produce severe constipation and abdominal discomfort. Clinicians should maintain a broad differential when CF patients develop new GI symptoms after GLP-1 initiation, recognizing that these may represent pharmacologic intolerance rather than disease progression. Early recognition and medication discontinuation can prevent unnecessary imaging, invasive evaluation, or hospitalization. This case highlights the importance of a physiology-informed approach when introducing novel metabolic therapies in patients with multisystem disorders. Collaboration among endocrinology, gastroenterology, and CF care teams is essential to individualize management strategies. Ultimately, this report contributes to the limited literature on GLP-1 receptor agonist use in CF and emphasizes that medications well tolerated in the general population may exert amplified or atypical effects in individuals with complex gastrointestinal physiology. This abstract is funded by: None