What is the role of gliflozins (sodium-glucose cotransporter 2 inhibitors) in the management of ascites?

Role of Gliflozins in Ascites Management

Gliflozins (SGLT2 inhibitors) are not currently recommended as primary therapy for ascites management in cirrhosis but may have a beneficial adjunctive role in reducing the risk of serious liver events in cirrhotic patients already on standard diuretic therapy. 1

Current Standard Management of Ascites

The management of ascites in cirrhosis follows a well-established approach:

First-line Treatment

• Dietary sodium restriction: No-added salt diet limited to 90 mmol/day (5.2 g salt/day) 2
• Diuretic therapy:
  • Start with spironolactone alone (100 mg/day, increasing to 400 mg/day as needed) 2
  • Add furosemide (up to 160 mg/day) if spironolactone alone is insufficient 2, 3

Second-line Treatment

• Therapeutic paracentesis: First-line for patients with large or refractory ascites 2
  • For paracentesis >5L: Albumin infusion (8g albumin/L of ascites removed) is required 2
  • For paracentesis <5L: Albumin may be considered in patients with ACLF or high risk of post-paracentesis AKI 2

Third-line Treatment

• TIPSS (Transjugular Intrahepatic Portosystemic Shunt): Should be considered in patients with refractory ascites 2
  • Caution needed in patients with age >70 years, bilirubin >50 μmol/L, platelet count <75×109/L, MELD score ≥18, current hepatic encephalopathy, active infection, or hepatorenal syndrome 2

Emerging Role of Gliflozins in Ascites

Recent evidence suggests SGLT2 inhibitors may provide benefits in patients with cirrhosis and ascites:

• A 2025 cohort study demonstrated that cirrhotic patients receiving SGLT2 inhibitors plus standard diuretics (furosemide and spironolactone) had a significantly lower incidence of serious liver events compared to those on standard diuretics alone (HR 0.68,95% CI 0.66-0.71) 1

• Specific benefits included reduced risk of:

  • Hepatorenal syndrome (HR 0.47) 1
  • Spontaneous bacterial peritonitis (HR 0.55) 1
  • Need for paracentesis (HR 0.54) 1
  • Variceal bleeding (HR 0.79) 1
  • All-cause hospitalizations (HR 0.67) 1

Mechanism of Action in Ascites

SGLT2 inhibitors work through multiple mechanisms that may benefit patients with ascites:

1. Natriuretic effect: Inhibit sodium reabsorption in the proximal tubule, though this effect may not be sustained long-term 4

2. Pleiotropic effects: Reduction of fibrosis, inflammation, and reactive oxygen species 5

3. Cardiovascular benefits: Reduction in heart failure hospitalizations, which may indirectly benefit patients with ascites due to cardiac causes 6

Important Considerations and Limitations

• SGLT2 inhibitors should be considered as adjunctive therapy to standard diuretic treatment, not as replacement 1

• A 2023 study found that SGLT2 inhibitors do not produce durable natriuresis or objective decongestion in heart failure patients 4, suggesting their benefits in ascites may work through alternative mechanisms

• Current guidelines on ascites management do not specifically recommend SGLT2 inhibitors 2

• Caution is needed in patients with severe hyponatremia, as SGLT2 inhibitors may potentially worsen this condition 7

Practical Approach to Using Gliflozins in Ascites

1. Start with standard therapy:

   • Sodium restriction
   • Spironolactone ± furosemide
   • Therapeutic paracentesis as needed

2. Consider adding an SGLT2 inhibitor in patients:

   • With concurrent type 2 diabetes or heart failure
   • At high risk for serious liver events
   • Already on optimal diuretic therapy but with suboptimal response

3. Monitor closely for:

   • Electrolyte abnormalities, particularly hyponatremia
   • Renal function
   • Volume status and blood pressure

Conclusion

While gliflozins show promise in reducing serious liver events in cirrhotic patients with ascites, they should be considered as an adjunct to, rather than a replacement for, established treatments. The most recent evidence suggests they may have a role in comprehensive management, particularly in patients with comorbid conditions like diabetes or heart failure, but further research is needed to establish their definitive place in treatment algorithms for ascites.