P4311 - 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

Laith Alomari, MD¹, Zaid Al-Fakhouri, MD², Ahmad Abdulraheem, MD³, Tinsae Anebo, MD⁴, Emmanuel Otabor, MBBS¹, Justin Lam, MD¹, Daniel M. Simadibrata, MD², Chidera Onwuzo, MBBS⁵, Ahmed A. Abdulelah, MD⁶, Thai Hau Koo, MD⁷, Jana Alomari, MS⁸, Karecia Byfield, MBBS⁹, Fnu Deepali, MD⁹
1Thomas Jefferson University, Philadelphia, PA; 2Case Western Reserve University / MetroHealth, Cleveland, OH; 3MedStar Washington Hospital Center, Washington, DC; 4Jefferson Einstein Hospital/Thomas Jefferson University, Philadelphia, PA; 5SUNY Upstate Medical University Hospital, Syracuse, NY; 6Royal Papworth Hospital, Cambridge, England, United Kingdom; 7University of Sciences Malaysia Specialist Hospital, Kelantan, Kelantan, Malaysia; 8Jordan University of Science and Technology, Irbid, Irbid, Jordan; 9Jefferson Einstein Hospital, Philadelphia, PA

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 two 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).

Discussion: 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.

Disclosures:
Laith Alomari indicated no relevant financial relationships.
Zaid Al-Fakhouri indicated no relevant financial relationships.
Ahmad Abdulraheem indicated no relevant financial relationships.
Tinsae Anebo indicated no relevant financial relationships.
Emmanuel Otabor indicated no relevant financial relationships.
Justin Lam indicated no relevant financial relationships.
Daniel Simadibrata indicated no relevant financial relationships.
Chidera Onwuzo indicated no relevant financial relationships.
Ahmed Abdulelah indicated no relevant financial relationships.
Thai Hau Koo indicated no relevant financial relationships.
Jana Alomari indicated no relevant financial relationships.
Karecia Byfield indicated no relevant financial relationships.
Fnu Deepali indicated no relevant financial relationships.

Laith Alomari, MD¹, Zaid Al-Fakhouri, MD², Ahmad Abdulraheem, MD³, Tinsae Anebo, MD⁴, Emmanuel Otabor, MBBS¹, Justin Lam, MD¹, Daniel M. Simadibrata, MD², Chidera Onwuzo, MBBS⁵, Ahmed A. Abdulelah, MD⁶, Thai Hau Koo, MD⁷, Jana Alomari, MS⁸, Karecia Byfield, MBBS⁹, Fnu Deepali, MD⁹. P4311 - 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, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.