S233 Impact of GLP-1 Receptor Agonists on Transplant-Free Survival and Hepatic Outcomes in Diabetic Patients With Primary Biliary Cholangitis: A Real-World Multicenter Analysis

Introduction: GLP-1 receptor agonists (GLP-1 RAs) are widely used agents with metabolic and anti-inflammatory effects. Experimental studies suggest that GLP-1 signaling supports cholangiocyte adaptation to cholestasis, a key feature of primary biliary cholangitis (PBC), by promoting cholangiocyte proliferation and function. Despite this potential hepatoprotective role, no clinical studies have assessed the impact of GLP-1 RAs in patients with both PBC and type 2 diabetes (T2DM). This study aimed to evaluate the association of GLP-1 RA use with transplant-free survival and hepatic decompensation events in this population. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network. Adult patients with T2DM and a diagnosis of PBC who were receiving ursodeoxycholic acid were included. Patients with a hemoglobin A1c >10%, as well as those with other chronic liver diseases were excluded. The study cohort was divided into 2 groups: the exposure group included patients treated with GLP-1 RAs, while the control group included patients receiving other glucose-lowering therapies, including insulin. Propensity score matching was performed based on demographics, comorbidities (including cardiovascular disease and chronic kidney disease), and BMI. Outcomes assessed included transplant-free survival, all-cause mortality, and a composite outcome of hepatic decompensation (defined as the development of hepatic encephalopathy, ascites, spontaneous bacterial peritonitis, or variceal bleeding). Results: After propensity score matching, 509 patients were included in each group. Transplant-free survival was significantly higher among GLP-1 RA users compared to controls (10 vs 14 events; HR: 0.25; 95% CI: 0.07–0.88; P = 0.020). Hepatic decompensation occurred in 23 patients in the GLP-1 RA group and 51 patients in the control group, with a significantly lower risk among GLP-1 RA users (HR: 0.57; 95% CI: 0.35–0.95; P = 0.027). All-cause mortality was also reduced in the GLP-1 RA group (31 vs 138 deaths; HR: 0.33; 95% CI: 0.22–0.49; P < 0.001). Conclusion: In this large real-world study of diabetic patients with PBC, use of GLP-1 RA was associated with significantly improved transplant-free survival, lower rates of hepatic decompensation, and reduced all-cause mortality compared to other glucose-lowering therapies. These findings support a potential protective role for GLP-1 RAs in patients with cholestatic liver disease and warrant further investigation.