Patterns of prescription and discontinuation of glucagon-like peptide-1 receptor agonists among patients with irritable bowel syndrome.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are associated with gastrointestinal (GI) adverse effects, but real-world evidence about their incidence in patients with functional GI disorders is limited. We examined their prescription and discontinuation patterns in irritable bowel syndrome (IBS) patients. METHODS: In this retrospective analysis of GLP-1RAs prescribed to patients with IBS at our institution from 2013-2023, we assessed the association of IBS subtype- and patient-related (age, race, body mass index, insurance, diabetes, gastroesophageal reflux disease) factors on the number and reasons for agent switches throughout the treatment course. RESULTS: Of the 256 patients with IBS prescribed >1 GLP-1RAs, 227 (88.7%) patients trialed 2-3 GLP-1RAs, while 29 (11.3%) trialed ≥4 agents. Mixed-type IBS patients showed the highest rates of switching, followed by constipation- and diarrhea-predominant type IBS (21.7%, 11.7% and 2.2%, respectively; P=0.02). Semaglutide had more discontinuations within 6 months of starting the first GLP-1RA, compared to liraglutide (63.4% vs. 43%; P=0.012). Patients aged ≥65 years were more likely to continue the first agent for >6 months compared to those <65 years (65.8% vs. 44%, P=0.014). In successive lines of therapy, treatment-related discontinuations (injection burden, non-response) remained fairly constant (17%, 14%, 14%) but symptom-related (nausea, vomiting, diarrhea, constipation) discontinuations increased steadily from first to third agent (28%, 30%, 48%, respectively). Patients with Medicare/Medicaid were more likely to switch ≥3 therapies, than those with private/self-pay coverage (23% vs. 7.3%; P=0.006). CONCLUSION: Our findings highlight the importance of tailoring therapy based on drug-specific and patient-related factors to optimize GLP-1RA use in IBS.