S269 Comparative Risk of Cholangiocarcinoma With GLP-1 Receptor Agonists and Bariatric Surgery in Patients With Diabetes and Obesity: A Matched Cohort Study

Introduction: Cholangiocarcinoma (CCA) is a rare but aggressive bile duct cancer with rising global incidence. Type 2 diabetes mellitus (T2DM) and obesity are independent risk factors for CCA. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and bariatric surgery are commonly used for glycemic and weight control in this population. While GLP-1 RAs offer clear metabolic benefits, prior studies have reported variable associations with gastrointestinal malignancies, including CCA. This study compares CCA risk in patients treated with GLP-1 RAs vs those who underwent bariatric surgery. Methods: We conducted a retrospective cohort study using the TriNetX database to identify adults (age ≥18) with T2DM and BMI >30 who initiated GLP-1 RA therapy or underwent bariatric surgery. A secondary analysis included patients with BMI >35, regardless of diabetes status. Patients with a prior history of CCA were excluded. Propensity score matching was applied in a 1:1 ratio to balance GLP-1 RA users and bariatric surgery patients on key characteristics. We adjusted for CCA risk factors and other diabetes- or obesity-related medications. The primary outcome was CCA incidence post-intervention. Risk was further stratified by age and sex. Adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) were estimated via Cox proportional hazards models. Results: A total of 94,452 patients who initiated GLP-1 RA therapy and 23,515 who underwent bariatric surgery were identified. After propensity score matching, 19,851 patients remained in each group. In the cohort with T2DM and BMI >30, GLP-1 RAs showed significantly lower risk of CCA compared to bariatric surgery (aHR = 0.45, 95% CI: 0.28–0.73; P = 0.01). Subgroup analysis showed this association was significant in women (aHR = 0.37, 95% CI: 0.17–0.77; P = 0.01) and in patients over age 45 (aHR = 0.49, 95% CI: 0.30–0.80; P = 0.01), but not in men (aHR = 0.59, 95% CI: 0.29–1.18; P = 0.13). Among those with BMI >35, GLP-1 RAs were also associated with a lower risk of CCA (aHR = 0.59, 95% CI: 0.35–0.99; P = 0.04). Conclusion: In this large real-world cohort, GLP-1 receptor agonists were associated with a significantly lower risk of CCA compared to bariatric surgery among patients with obesity and T2DM. These findings highlight a potential association between GLP-1 RA use and lower CCA risk, warranting further prospective studies to confirm causality and explore underlying biological mechanisms.