Is dapagliflozin (Forxiga) safe to use in patients with advanced liver cirrhosis?

Dapagliflozin Use in Advanced Liver Cirrhosis

Dapagliflozin can be used with caution in Child-Pugh class A and B cirrhosis but should be avoided in Child-Pugh class C (decompensated) cirrhosis, where insulin is the preferred glucose-lowering agent. 1, 2

Risk Stratification by Child-Pugh Class

Child-Pugh Class A (Compensated Cirrhosis)

• Dapagliflozin 10 mg daily is safe and appropriate for treating type 2 diabetes in this population 1, 3
• The European Association for the Study of the Liver (EASL) specifically lists dapagliflozin as a first-line agent for diabetic patients with compensated cirrhosis 1
• No dose adjustment required based on hepatic impairment alone 4

Child-Pugh Class B (Compensated but More Advanced)

• Dapagliflozin can be used but requires close monitoring for acute kidney injury and infections 1
• EASL provides a weak recommendation with consensus-level evidence (LoE 4) for this population 1
• Consider reducing dose to 5 mg daily in more advanced Child-Pugh B patients 3
• A recent study showed improved ascites control and reduced diuretic requirements in Child-Pugh B patients, though with increased risk of AKI (50% vs 15%) and infections (55% vs 20%) 5

Child-Pugh Class C (Decompensated Cirrhosis)

• Dapagliflozin should be avoided entirely 1, 2
• Insulin is the preferred glucose-lowering agent, though it requires careful monitoring to avoid hypoglycemia 1, 6
• The FDA label states that safety and efficacy have not been specifically studied in severe hepatic impairment, and benefit-risk should be individually assessed 4

Critical Safety Considerations

Acute Kidney Injury Risk

• Patients with cirrhosis are at baseline higher risk for volume depletion and acute kidney injury 4, 7
• In a recent pilot study, AKI occurred in 50% of dapagliflozin-treated patients versus 15% on placebo 5
• Monitor renal function closely, especially in patients with ascites or on diuretics 1, 5

Infection Risk

• Cirrhotic patients have baseline immune dysfunction 7
• Dapagliflozin increases urinary glucose excretion, which may theoretically increase urinary tract infection risk 4
• One study showed significantly higher infection rates (55% vs 20%) in dapagliflozin-treated cirrhotic patients 5
• Monitor for signs of urinary tract infections and genital mycotic infections 4, 5

Volume Status and Diuretics

• Dapagliflozin causes natriuresis and osmotic diuresis, which can be beneficial for ascites but risky in volume-depleted patients 4, 5
• In one study, dapagliflozin reduced the need for diuretic dose escalation and improved ascites control 3
• However, another study showed no improvement in survival despite better ascites control 5
• Carefully balance diuretic doses when initiating dapagliflozin to avoid excessive volume depletion 3, 5

Practical Dosing Algorithm

For Child-Pugh A:

• Start dapagliflozin 10 mg daily 3
• Monitor renal function at baseline, 1 week, and monthly for 3 months 1
• Check for signs of infection at each visit 5

For Child-Pugh B:

• Consider starting with 5 mg daily, especially if eGFR 25-45 mL/min/1.73 m² 8, 3
• May increase to 10 mg if tolerated after 2-4 weeks 3
• More frequent monitoring: renal function weekly for first month, then biweekly 1
• Assess volume status and adjust diuretics as needed 3, 5

For Child-Pugh C:

• Do not use dapagliflozin 1, 2
• Use insulin with careful glucose monitoring to avoid hypoglycemia 1, 6

Alternative Glucose-Lowering Agents in Cirrhosis

Metformin

• Can be used in compensated cirrhosis with eGFR >30 mL/min 8, 1
• Absolutely contraindicated in decompensated cirrhosis due to lactic acidosis risk 1, 6

GLP-1 Receptor Agonists

• Safe in Child-Pugh class A cirrhosis 1, 6
• Should be avoided in decompensated cirrhosis 1
• May be preferable to dapagliflozin in patients with infection concerns 6

Pioglitazone

• Proven efficacy for NASH with fibrosis reversal 8, 2
• Contraindicated in decompensated cirrhosis 8, 2
• Can be combined with dapagliflozin to mitigate weight gain in compensated cirrhosis 8

Common Pitfalls to Avoid

• Do not assume dapagliflozin is safe in all cirrhosis: Child-Pugh classification is critical for decision-making 1, 3
• Do not ignore baseline renal function: eGFR <25 mL/min/1.73 m² is a relative contraindication even in compensated cirrhosis 8, 4
• Do not overlook volume status: Patients on high-dose diuretics or with refractory ascites are at higher AKI risk 5, 7
• Do not forget infection surveillance: The combination of cirrhosis-related immune dysfunction and glycosuria increases infection risk 5, 7
• Do not expect mortality benefit: While dapagliflozin may improve ascites control, current evidence shows no survival benefit in cirrhosis 5

Emerging Evidence

A 2024 pilot study with empagliflozin (another SGLT2 inhibitor) showed safety and tolerability in advanced chronic liver disease, with adverse event rates similar to phase 3 trials in non-cirrhotic populations 9. However, a 2025 dapagliflozin study showed concerning increases in AKI and infections despite improved ascites control 5. This conflicting evidence suggests that while SGLT2 inhibitors may be used in compensated cirrhosis, they require vigilant monitoring and may not be appropriate for all patients with advanced disease.