Abstract / Summary
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) suppress intestinal motility, raising concerns regarding impaired bowel preparation quality during colonoscopy. Given the widespread use of these agents and inconsistent societal guidelines regarding their peri-procedural management, this study aimed to determine whether GLP-1 RA exposure meaningfully increases the likelihood of undergoing an early repeat colonoscopy, a clinical surrogate for inadequate bowel preparation. This retrospective cohort study utilized the TriNetX US Collaborative Network to identify adult patients with type 2 diabetes mellitus who underwent a colonoscopy between January 1, 2020, and February 1, 2025. Patients prescribed a GLP-1 RA within 3 months prior to the procedure were compared to a control cohort without GLP-1 RA exposure. To balance baseline characteristics, 1:1 propensity score matching was performed across a robust set of demographic, clinical, and pharmacological covariates. The primary outcome was the occurrence of a repeat colonoscopy within 12 months, analyzed using Kaplan-Meier survival analysis and Cox proportional hazards models. Pre-specified negative control outcomes and exposures were incorporated to mitigate unmeasured confounding. Following propensity score matching, 4,870 patients were included in each cohort. During the 1-year follow-up, the GLP-1 RA cohort demonstrated a higher risk of repeat colonoscopy compared to the control group (11.0% vs. 8.9%; absolute risk difference [ARD], 2.16%; Hazard Ratio [HR], 1.371; 95% CI, 1.208–1.556; P = 0.0004). No increased risks were observed across multiple negative control outcomes. The elevated risk pattern was consistent across 1-, 3-, 6-, and 12-month follow-up windows. Notably, temporal stratification revealed that this association persisted without attenuation even after the June 2023 introduction of societal guidelines recommending peri-procedural GLP-1 RA withholding (post-guideline HR, 1.366; 95% CI, 1.132–1.647). GLP-1 RA therapy is significantly associated with an elevated risk of requiring a repeat colonoscopy among patients with type 2 diabetes mellitus, although the absolute risk difference is modest. These findings highlight potential downstream clinical patterns associated with GLP-1 RA use and underscore a need for further evaluation of standardized, agent-specific peri-procedural protocols.