Keywords
GLP-1 receptor agonists
SGLT2 inhibitors
Comparative effectiveness
Hepatic decompensation
Ascites
Data Availability Statement
Data were obtained from the TriNetX US Collaborative Network. Access to these data is restricted to researchers at member institutions with a valid data-use agreement. Interested parties may contact TriNetX (https://trinetx.com/) for information regarding data access.
How to Cite
Abstract
Background: Cirrhosis and metabolic comorbidities frequently coexist. Both glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) have shown cardiometabolic and hepatic benefits, but their comparative effectiveness in established cirrhosis remains unclear. We compared 1-year clinical outcomes between adults with cirrhosis initiating either class.
Methods: Using the TriNetX U.S. Collaborative Network, we identified adults with cirrhosis who initiated a GLP-1RA or SGLT2i after diagnosis and had no prior exposure to the comparator class. One-to-one propensity score matching balanced demographic, clinical, medication, and laboratory covariates. Primary outcomes at 1 year were all-cause mortality and inpatient hospitalization. Secondary outcomes included individual and composite cirrhosis decompensation events (ascites, paracentesis, spontaneous bacterial peritonitis, variceal bleeding, hepatic encephalopathy, hepatorenal syndrome) and adverse events (acute kidney injury, hypoglycemia, acute pancreatitis).
Results: The matched cohorts comprised 8,016 patients per arm. GLP-1RA users had lower 1-year all-cause mortality (4.3% vs 5.3%; OR 0.80, 95% CI 0.69–0.93; p=0.003) and fewer composite decompensation events (5.3% vs 6.7%; OR 0.78, 95% CI 0.69–0.88; p<0.0001), driven by reductions in ascites and spontaneous bacterial peritonitis. Hospitalization did not differ (7.6% vs 8.2%; p=0.3). Variceal bleeding, hepatic encephalopathy, and hepatorenal syndrome were comparable. AKI was less frequent with GLP-1RAs (4.8% vs 6.2%; p=0.001); rates of hypoglycemia and pancreatitis were similar.
Conclusions: In this large real-world analysis of adults with cirrhosis, initiation of a GLP-1RA was associated with lower 1-year mortality and fewer ascites-related decompensation and AKI events compared with initiation of an SGLT2i.
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Copyright (c) 2026 Hatem Ahmed, Imad Alabdul Razzak, Eyad Abdulrazzak, Sameh Gomaa, Motaz Almahmood, Khloud Abdelrazeq, Joelle Lauchner