S2901 Comparative Outcomes of GLP-1 Receptor Agonists vs SGLT2 Inhibitors in Patients With Cirrhosis

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) are widely used antidiabetic agents that are associated with cardiovascular and renal benefits in patients with type 2 diabetes. Growing evidence demonstrates benefits of GLP-1 RAs in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). SGLT2 inhibitors are also linked to improvements in liver-related metrics in MASLD, including among patients with cirrhosis. However, direct comparisons in cirrhosis are limited. This study compared 1-year outcomes between GLP-1RA and SGLT2i users with cirrhosis. Methods: We conducted a retrospective multicenter cohort study using TriNetX to identify adults with cirrhosis prescribed GLP-1RA or SGLT2i. Propensity score matching was used to balance baseline characteristics. Primary outcomes were 1-year mortality and hospitalization rates. Secondary outcomes included hepatic decompensation events: ascites, spontaneous bacterial peritonitis (SBP), variceal bleeding, hepatic encephalopathy, jaundice, hepatocellular carcinoma (HCC), and paracentesis rates. Tertiary outcomes included liver and renal biomarkers. Adverse events were also assessed. Results: After matching, 8,847 patients remained per cohort. At 1 year, GLP-1RA use was associated with lower all-cause mortality (4.3% vs 5.3%; OR 0.801; 95% CI: 0.693–0.927; P = 0.003) and fewer hepatic decompensation events (5.7% vs 7.1%; OR 0.788; P = 0.001), including ascites (OR 0.691; P < 0.0001), need for paracentesis (OR 0.583; P < 0.0001), and SBP (OR 0.620; P = 0.023). No significant differences were observed in variceal bleeding, HCC, or hepatic encephalopathy. GLP-1RA users also had lower rates of acute kidney injury (4.8% vs 6.2%; OR 0.763; P = 0.001). Adverse event rates, including hypoglycemia and pancreatitis, were similar. Tertiary outcomes showed modest but statistically significant improvements in aspartate aminotransferase, alanine aminotransferase, albumin, and INR levels in the GLP-1RA group. No significant differences were found in bilirubin, creatinine, or sodium levels. Conclusion: Among adults with cirrhosis, GLP-1 receptor agonists were linked to lower 1-year all-cause mortality and reduced rates of ascites, spontaneous bacterial peritonitis, and paracentesis compared with SGLT2 inhibitors. They also produced modest improvements in aspartate aminotransferase, alanine aminotransferase, albumin, and INR. These real-world data suggest GLP-1RAs may offer broader hepatic benefits than SGLT2 inhibitors in this high-risk population.