Impact of GLP-1 Analogue Therapy on Gastrointestinal Outcomes in Patients with Irritable Bowel Syndrome: A Real-World TriNetX Analysis.

BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists are increasingly prescribed for diabetes and obesity, conditions that frequently coexist with irritable bowel syndrome (IBS). Their effects on gastrointestinal motility and visceral sensitivity raise the possibility of therapeutic benefit in IBS, but real-world evidence remains limited. This study evaluated the association between GLP-1 receptor agonist initiation and subsequent gastrointestinal outcomes in patients with IBS using a large federated electronic health records network. METHODS: We conducted a retrospective cohort study using the TriNetX Research Network. Patients with IBS (ICD-10 K58) who initiated GLP-1 receptor agonists (semaglutide, liraglutide, dulaglutide, exenatide, or tirzepatide) within 30 or 90 days after IBS diagnosis (GLP-1 group) were propensity score matched to IBS patients who did not receive GLP-1 therapy (non-GLP-1 group). Analyses were performed for the overall IBS cohort and stratified by subtype (IBS-D [K58.0] and IBS-C [K58.1]). Outcomes included coded chronic diarrhea, chronic constipation, abdominal pain, malabsorption, and abdominal bloating/distension. Incident outcomes were assessed using risk ratios, hazard ratios from Kaplan-Meier survival analysis, and log-rank tests. RESULTS: After matching, the 30-day landmark cohort included 4,668 patients per group and the 90-day landmark cohort included 6,665 patients per group. In the 90-day analysis, GLP-1 use was associated with significantly lower rates of chronic diarrhea (8.9% vs. 10.6%), chronic constipation (19.8% vs. 22.0%), abdominal pain (31.6% vs. 35.8%), and abdominal bloating/distension (8.3% vs. 10.9%) compared with non-GLP-1 controls (all p < 0.001). Similar reductions were observed in IBS-D and IBS-C subtypes, particularly for abdominal pain and bloating/distension. Differences in outcome recurrence (number of instances) were smaller than differences in incidence. CONCLUSIONS: Initiation of GLP-1 receptor agonists was associated with significantly lower rates of several coded gastrointestinal symptoms in patients with IBS across multiple landmark periods and subtypes. While these observational findings are hypothesis-generating and require confirmation in prospective studies, they suggest potential benefit of GLP-1 therapies on IBS-related outcomes.