S3058 Comparative Risk of Small Intestinal Bacterial Overgrowth (SIBO) Among Patients Using GLP-1 Receptor Agonists: A Real-World Analysis Using TriNetX

Introduction: Glucagon-like peptide-1 (GLP-1) is a gut-derived incretin hormone, offering benefits such as weight loss and improved glycemic control. These agents slow gastric emptying and intestinal transit, which theoretically could predispose to small intestinal bacterial overgrowth (SIBO). However, there is no defining link to establish GLP-1 receptor agonist agents as a direct cause of SIBO. Our study aims to explore the relationship between GLP-1 RA and the development of SIBO. Methods: A retrospective cohort study was conducted using the TriNetX Research Network, a federated database comprising de-identified electronic health records from multiple healthcare organizations. Adult patients prescribed a GLP-1 RA (albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide, or tirzepatide) between January 2010 and May 2025 were included. Patients with prior diagnoses or procedures known to affect gastrointestinal motility (e.g. gastroparesis, bowel resections), and conditions that could interfere with breath testing accuracy (e.g., lactose intolerance, fructose intolerance) were excluded. The primary outcome was a new diagnosis of SIBO following GLP-1 RA exposure. Incidence rates were calculated for each agent individually. Results: A total of 2,305,630 patients were analyzed. The incidence of SIBO varied across the different GLP-1 receptor agonist agents. Albiglutide demonstrated the highest risk (0.156%), while tirzepatide showed the lowest (0.022%). Intermediate risks were observed for exenatide (0.048%), dulaglutide (0.047%), liraglutide (0.055%), and lixisenatide (0.073%). Semaglutide, despite the largest cohort (n = 992,660), had a relatively low risk (0.039%). Kaplan-Meier analysis confirmed temporal consistency (P < 0.05 for all agents). Conclusion: The overall risk of developing SIBO among GLP-1 receptor agonist users was low but variable across agents. This variability in SIBO risk among GLP-1 agonists, reflects potential differences in pharmacokinetics (e.g., albiglutide's weekly administration vs exenatide's shorter half-life). The elevated risk with albiglutide and lixisenatide may relate to prolonged gastric emptying effects, while trizepatide's GIP/GLP-1 dual agonism might offer protective mechanisms. Further studies are warranted to better characterize this potential adverse effect and guide agent selection in patients at risk for SIBO.