Association between GLP-1 receptor agonist use and risk of repeat colonoscopy: a real-world cohort study with exploratory discontinuation analyses

Abstract While glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used for diabetes and obesity, their effects on gastrointestinal motility have raised concern about colonoscopy outcomes. We evaluated the association between GLP-1 RA use and repeat colonoscopy and performed exploratory analyses of pre-procedural discontinuation intervals. We conducted a retrospective cohort study using the TriNetX Global Collaborative Network. The analysis was restricted to adults aged 18–90 years with an index procedure between January 2021 and January 2025. Long-term GLP-1 RA users were propensity-score matched 1:1 with non-users on 44 covariates. The primary outcome was repeat colonoscopy within 12 months. Stratified analyses, exploratory analyses of discontinuation intervals from 0 to 8 weeks, and active-comparator analyses against dipeptidyl peptidase-4 (DPP-4) inhibitor and sodium-glucose co-transporter 2 (SGLT2) inhibitor users were also performed. After propensity-score matching, 20,490 GLP-1 RA users were compared with 20,490 non-users. GLP-1 RA use was associated with a higher risk of repeat colonoscopy within 12 months (RR 1.50, 95% CI 1.39–1.61), with similar associations at 6 months (RR 1.61, 95% CI 1.48–1.75), 3 months (RR 1.75, 95% CI 1.59–1.94), and 2 months (RR 1.86, 95% CI 1.66–2.08). In active-comparator analysis, the association persisted versus DPP-4 inhibitors (RR 1.41, 95% CI 1.21–1.63) and SGLT2 inhibitors (RR 1.26, 95% CI 1.15–1.38). Exploratory discontinuation estimates attenuated with longer intervals, but overlapping confidence intervals and decreasing stratum sizes did not identify a definitive discontinuation threshold. GLP-1 RA use was associated with a higher likelihood of repeat colonoscopy within one year in a contemporary, propensity-score-matched cohort, including in active-comparator analyses. Because repeat colonoscopy is a non-specific healthcare-utilization outcome and the discontinuation analyses were observational and exploratory, these findings do not establish inadequate bowel preparation as the mechanism or support a specific pre-procedural discontinuation interval. Prospective studies with directly measured bowel-preparation quality are needed.