What are the considerations for using Sodium-Glucose Linked Transporter 2 (SGLT2) inhibitors in patients with cirrhosis?

SGLT2 Inhibitors in Cirrhosis: Clinical Considerations

SGLT2 inhibitors can be used in patients with Child-Pugh class A and B cirrhosis but should be avoided in decompensated cirrhosis due to risks of hemodynamic instability and acute kidney injury. 1

Patient Selection and Risk Stratification

• SGLT2 inhibitors are appropriate for patients with compensated (Child-Pugh A) cirrhosis, with evidence supporting their use in Child-Pugh B cirrhosis as well 1
• These medications should be avoided in patients with decompensated cirrhosis, especially when there is concomitant renal impairment, due to increased risk of complications 1, 2
• Renal function must be assessed before initiating therapy, with preserved renal function (GFR >30 ml/min) being a prerequisite for safe use 3

Potential Benefits in Cirrhosis

• Recent evidence suggests SGLT2 inhibitors may reduce the incidence of serious liver events in cirrhotic patients, including lower rates of ascites, variceal development, and hyponatremia 4
• SGLT2 inhibitors have shown improvement in liver function parameters in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) 5, 6
• They may offer benefits beyond glycemic control, including:
  • Reduction in hepatorenal syndrome (HR 0.47) 4
  • Decreased incidence of spontaneous bacterial peritonitis (HR 0.55) 4
  • Lower rates of paracentesis requirements (HR 0.54) 4
  • Improvement in renal function in patients with cirrhosis and type 2 diabetes 6

Management of Ascites

• SGLT2 inhibitors may help manage refractory ascites through multiple mechanisms including natriuresis and osmotic diuresis 7
• They appear to be particularly beneficial in patients with cirrhosis secondary to MASLD who have ascites 8
• The diuretic effect works through a mechanism different from traditional diuretics (loop diuretics and aldosterone antagonists), potentially offering synergistic benefits 7

Safety Considerations and Monitoring

• Close monitoring is essential when using SGLT2 inhibitors in cirrhosis, with particular attention to:
  • Hemodynamic status, as some studies report risk of hemodynamic instability 8
  • Renal function, with regular assessment of GFR and signs of acute kidney injury 2, 8
  • Electrolyte abnormalities, particularly sodium levels 8
  • Infection risk, which may be elevated in some patients 8

Comparative Medication Selection in Cirrhotic Patients with Diabetes

• Insulin remains the only evidence-based option for treating diabetes in patients with decompensated cirrhosis 3
• GLP-1 receptor agonists can be used in Child-Pugh class A cirrhosis only 3, 1
• Metformin can be used in compensated cirrhosis with preserved renal function but should be discontinued immediately if decompensation occurs or GFR falls below 30 mL/min 2, 1
• Sulfonylureas should be avoided in patients with hepatic decompensation due to increased risk of hypoglycemia 1, 3

Nutritional Considerations

• When using SGLT2 inhibitors in cirrhotic patients, ensure adequate nutritional support:
  • Provide 35 kcal/kg of body weight/day in patients with decompensated cirrhosis 2
  • Maintain protein intake of 1.2-1.5 g/kg of body weight/day to prevent sarcopenia 3, 2
  • Consider late evening snacks for patients with sarcopenia or decompensated cirrhosis 2

Common Pitfalls to Avoid

• Do not rely solely on HbA1c for diabetes monitoring in cirrhosis, especially with impaired liver function (Child-Pugh B-C) 3
• Avoid initiating SGLT2 inhibitors in patients with active infection or those at high risk for infection 8
• Be cautious about volume depletion, especially in patients already on diuretics, as this could precipitate acute kidney injury 2, 8
• Discontinue SGLT2 inhibitors immediately if liver decompensation occurs 2