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

Misha Gautam; Utkarsh Goel; Abbas Bader; Samiya Azim; Noor Hassan; Esmat Sadeddin; Wendell Clarkston; Hassan Ghoz

Authors Misha Gautam, Utkarsh Goel, Abbas Bader, Samiya Azim, Noor Hassan, Esmat Sadeddin, Wendell Clarkston, Hassan Ghoz.

Abstract

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.

Keywords Irritable bowel syndrome, subtypes, GLP-1 receptor agonists, real-world evidence

Ann Gastroenterol 2025; 38 (4): 420-427