S2676 Effects of GLP-1 Agonists on Rates of Decompensated Liver Failure

Introduction: Cirrhosis is a leading cause of morbidity and mortality, particularly when it progresses to decompensated cirrhosis marked by complications such as ascites, hepatic encephalopathy, and variceal bleeding. Obesity and type 2 diabetes (T2D), significantly increase the risk of developing metabolic dysfunction-associated steatotic liver disease (MASLD) and its more severe form, metabolic dysfunction-associated steatohepatitis (MASH), which are major drivers of cirrhosis progression. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown promise in improving metabolic parameters and decreasing inflammation in MASLD and MASH. However, their impact on the progression from compensated to decompensated cirrhosis remains poorly understood. This study evaluates whether GLP-1 RA use is associated with a reduced risk of decompensation in patients with metabolic liver disease. Methods: We conducted a retrospective cohort study of patients with obesity or type 2 diabetes who also had a diagnosis of MASLD or MASH. Patients were stratified based on GLP-1 RA prescription status. The primary outcome was hospitalization for decompensated cirrhosis. Secondary outcomes included cirrhosis diagnosis and rates of first and recurrent hospitalizations for decompensation. Results: A total of 2,188 patients were included in the study, with 852 (38.9%) in the GLP-1 RA group and 1,336 (61.1%) in the non-GLP-1 RA group. The average age of the cohort was 57.4 years (SD 15.6) for the non-GLP-1 group and 55.8 years (SD 12.9) for the GLP-1 group. The cohort was 47.1% woman and 27.4% man in the non-GLP-1 group, compared to 22.2% woman and 9.4% man in the GLP-1 group. The majority of patients were White (63.95% in the non-GLP-1 group and 22.8% in the GLP-1 group), followed by Black or African American patients (5.73% and 2.17%, respectively). GLP-1 RA use was associated with a significantly lower rate of decompensation compared to non-use (P < 0.05). Subgroup analysis indicated that rural patients had higher overall rates of decompensation. Conclusion: These findings suggest that GLP-1 RAs may provide a protective effect against decompensation in patients with metabolic associated liver disease. Given the rising prevalence of obesity, T2D, and MASLD/MASH, GLP-1 RAs could represent a promising therapeutic option to mitigate liver disease progression and reduce hospitalization rates. Further prospective studies are needed to confirm these associations and clarify the underlying mechanisms driving these benefits.