S190 Increased Risk of Gallbladder and Biliary Diseases With GLP-1 Receptor Agonists: A United States Collaborative Network Study

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly utilized for patients with type 2 diabetes mellitus (T2DM) and obesity. Recent evidence indicates that using GLP-1 RAs could increase the risk of gallbladder (GB) and biliary-related complications such as cholelithiasis and cholecystitis. The purpose of this study is to examine the GB and biliary diseases among T2DM patients treated with GLP-1 RAs compared to those not receiving GLP-1 RAs, using a large real-world dataset. Methods: A retrospective cohort study was conducted using the TriNet X database. Adults (≥18 years) with T2DM were identified between 2007 and 2020. Patients with history of bariatric surgery, gallbladder and biliary disease, hemolytic anemia, HIV or HIV medications, and pregnancy were excluded. Patients were then stratified into 2 cohorts: Cohort 1: patient received GLP-1 RAs and Cohort 2: patients received other oral diabetes medications. Propensity score matching (PSM) was utilized to balance baseline characteristics across the cohorts as shown in Table 1 [Tables presented at ACG annual meeting]. Outcomes were assessed at 2 and 3 years after initiating GLP-1 RAs. Study outcomes were cholelithiasis, choledocholithiasis, cholecystitis, cholangitis, cholecystectomy, or endoscopic retrograde cholangiopancreatography procedures. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were calculated for each outcome. Results: Before PSM, there was a total of 32,299 patients in GLP-1 RAs group, while 120,948 patients in control group. After matching, each cohort consisted of 31,524 patients. At the 2-year follow-up, patients in the GLP-1 RAs group had a significantly increased risk of cholelithiasis (aOR 1.29; 95% CI: 1.08–1.55; P = 0.005), while the rates of choledocholithiasis, cholecystitis, cholangitis, cholecystectomy, and endoscopic retrograde cholangiopancreatography procedures were not significant between the cohorts. By 3 years, the GLP-1 RAs group had significantly greater risks of cholelithiasis (aOR 1.35; 95% CI: 1.32–1.56; P < 0.01), choledocholithiasis (aOR 1.82; 95% CI: 1.10–3.11; P = 0.02), and cholecystitis (aOR 1.42; 95% CI: 1.11–1.87; P = 0.01), whereas the risks of cholangitis and procedural interventions remained non-significant between the cohorts. Conclusion: GLP-1 RAs are associated with increased risk of GB and biliary diseases in patients with T2DM, with this risk increasing over time. These findings underscore the importance of screening patients with high risk for pre-existing gall bladder disease prior to and during GLP-1 RAs therapy.