GLP-1RA Discontinuation Among Veterans With Type 2 Diabetes and Irritable Bowel Syndrome

OBJECTIVE To examine whether coexisting irritable bowel syndrome (IBS) is associated with an increased risk of glucagon-like peptide 1 receptor agonist (GLP-1RA) discontinuation among veterans with type 2 diabetes. RESEARCH DESIGN AND METHODS Using national Veterans Health Administration administrative data (2018–2023), we identified 245,084 veterans with type 2 diabetes initiating a GLP-1RA. Two cohorts were defined: type 2 diabetes only and coexisting type 2 diabetes and IBS. The primary outcome was GLP-1RA discontinuation within 1 year of initiation. Discontinuation risk was compared using χ2 tests and Cox proportional hazards (CPH) regression, adjusting for demographics and clinical variables. RESULTS Among GLP-1RA initiators, 2,178 (0.9%) had coexisting IBS. Overall, 63,335 (24.8%) discontinued GLP-1RA therapy within 1 year. Rates of discontinuation were lower among veterans with IBS (491 of 2,178 [22.5%]) compared with those without IBS (62,844 of 242,906 [25.9%]) (P < 0.001). In an unadjusted CPH model, IBS was associated with a lower risk of discontinuation (hazard ratio [HR] 0.88, 95% CI 0.80–0.96), but the association was not statistically significant after adjustment (adjusted HR 0.93, 95% CI 0.85–1.01). Several covariates, including BMI, concurrent glucose-lowering therapy, depressive disorders, GLP-1RA type, and initiation year, were independently associated with discontinuation. CONCLUSIONS In a large national cohort of veterans with type 2 diabetes, IBS was not associated with higher GLP-1RA discontinuation risk after adjustment for demographic and clinical characteristics. These findings challenge assumptions that gastrointestinal comorbidities universally heighten GLP-1RA intolerance and suggest that IBS symptom experience or self-management may support persistence. Clinical decisions should consider patient comorbidity profiles, treatment burden, and symptom management experiences to optimize GLP-1RA continuation.