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S3216 Safety and Efficacy of Dapagliflozin in Ascites Management
Abstract   Peer reviewed

S3216 Safety and Efficacy of Dapagliflozin in Ascites Management

Zhexiang He, Ademola Ajibade, Thomas Elimihele, Abdullah Sohail, Antonio Sanchez, Sara Naimimohasses and Ishtiaq Ahmad
The American journal of gastroenterology, Vol.121(10S1), pp.S700-S700
10/01/2026
DOI: 10.14309/01.ajg.0001222116.25838.a9

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Abstract

Introduction: Cirrhosis is a global health challenge and a leading cause of liver-related mortality. Ascites, the most common manifestation of hepatic decompensation, is associated with reduced survival, frequent hospitalization, and complications including spontaneous bacterial peritonitis and hepatorenal syndrome. Standard management with spironolactone and furosemide is often limited by suboptimal efficacy and adverse effects. Sodium–glucose cotransporter-2 (SGLT2) inhibitors, such as dapagliflozin, have natriuretic and cardiorenal properties and may represent a novel adjunctive therapy for ascites management in cirrhosis. Methods: We performed a retrospective active-comparator, new-user cohort study using the TriNetX Global Collaborative Network. Adult patients (≥18 years) with past medical history of cirrhosis with ascites receiving diuretics were identified and categorized into spironolactone and furosemide or combination therapy with dapagliflozin, spironolactone, and furosemide. After applying exclusion criteria and 1:1 propensity score matching, 1,600 well-balanced matched pairs were included. Primary outcomes were all-cause mortality, hospitalization, and paracentesis at 1 and 3 years. Secondary outcomes included acute kidney injury (AKI), hepatorenal syndrome (HRS), spontaneous bacterial peritonitis (SBP), electrolyte abnormalities, and hypotension. Results: At 1 year, combination therapy was associated with lower all-cause mortality (13.8% vs 17.9%; HR 0.72, 95% CI 0.60–0.85; P < 0.001) and hospitalization (18.3% vs 22.6%; HR 0.73, 95% CI 0.63–0.86; P < 0.001), with no difference in paracentesis. At 3 years, mortality benefit persisted (25.0% vs 31.5%; HR 0.73, 95% CI 0.62–0.85; P < 0.001), and hospitalization remained lower (HR 0.79, 95% CI 0.68–0.93; P = 0.003). Combination therapy was also associated with reduced AKI at 1 year and lower severe hyponatremia at 3 years, without increased risk of hypotension, hyperkalemia, or HRS. Benefits were consistent across subgroups, particularly in patients with heart failure and type 2 diabetes. Conclusion: To our knowledge, this is the largest real-world analysis, showing that the addition of dapagliflozin to spironolactone-based therapy was associated with reduced mortality, hospitalization, and renal complications in patients with cirrhosis. These findings support the benefit of SGLT2 inhibitors as a promising adjunctive strategy for improving outcomes in cirrhotic patients with ascites, although prospective validation remains necessary.
 Ascites Combination therapy Hospitalization Hypotension Liver cirrhosis Mortality Peritonitis

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