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S2598 Long-Term Outcomes of GLP-1 Receptor Agonists Versus Metformin in Patients With Obesity and Cirrhosis: A Propensity-Matched Cohort Study
Abstract   Peer reviewed

S2598 Long-Term Outcomes of GLP-1 Receptor Agonists Versus Metformin in Patients With Obesity and Cirrhosis: A Propensity-Matched Cohort Study

M. Housam Nanah, Hussam Kawas, Amr Farwati, Mohamad Mahdi Osman, Omar T Sims and Dian J Chiang
The American journal of gastroenterology, Vol.121(10S1), pp.S567-S567
10/01/2026
DOI: 10.14309/01.ajg.0001219644.50457.9c

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Abstract

Introduction: Metabolic dysfunction–associated steatotic liver disease (MASLD) is highly prevalent among patients with obesity and cirrhosis. Although glucagon-like peptide-1 receptor agonists (GLP-1 RA) may provide hepatic benefits beyond weight loss, long-term comparative outcome data remain limited. We compared 10-year hepatic and systemic outcomes among patients with obesity and cirrhosis receiving GLP-1 RA therapy versus metformin. Methods: We conducted a retrospective multicenter cohort study using a large electronic health records database. Adults with obesity and cirrhosis receiving metformin or GLP-1 RA therapy were identified. After 1:1 propensity score matching, 10-year outcomes including mortality, acute pancreatitis, acute kidney failure, intrahepatic malignancy, liver transplantation, and hospital admissions/emergency department visits were assessed. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated. Results: After propensity score matching, 31,334 patients were included in each cohort. Mean follow-up was 1,184 days for metformin and 829 days for GLP-1 RA recipients. Compared with GLP-1 RA therapy, metformin was associated with higher hazards of mortality (HR 1.86, 95% CI 1.79–1.93), acute pancreatitis (HR 1.16, 95% CI 1.03–1.30), acute kidney failure (HR 1.34, 95% CI 1.28–1.40), intrahepatic malignancy (HR 1.14, 95% CI 1.05–1.23), and hospital admissions/ED visits (HR 1.25, 95% CI 1.19–1.30). No difference was observed in liver transplantation (HR 1.00, 95% CI 0.86–1.15). Event rates were 27.4% vs 11.5% for mortality, 2.5% vs 1.6% for acute pancreatitis, 26.3% vs 14.8% for acute kidney failure, 5.1% vs 3.4% for intrahepatic malignancy, 1.3% vs 1.0% for liver transplantation, and 27.6% vs 17.6% for hospital admissions/ED visits (metformin vs GLP-1 RA). Conclusion: In this large real-world propensity-matched cohort of patients with obesity and cirrhosis, GLP-1 RA therapy was associated with lower risks of mortality, acute pancreatitis, acute kidney failure, intrahepatic malignancy, liver transplantation, and healthcare utilization compared with metformin. These findings extend prior studies focused primarily on metabolic and glycemic outcomes by demonstrating favorable long-term clinical outcomes in a high-risk cirrhosis population. Overall, GLP-1 RA therapy was associated with a more favorable safety and complication profile than metformin in patients with obesity-associated cirrhosis.
 Cohort Analysis Emergency Medical Care Kidney Diseases Metabolism Obesity Agonists GLP-1 receptor agonists Liver cirrhosis Liver transplants Mortality Pancreatitis Patient admissions Weight control

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