Is saroglitazar indicated in MASLD (Metabolic Associated Steatohepatitis Liver Disease) related liver cirrhosis, specifically in compensated or decompensated cirrhosis?

Saroglitazar is NOT Indicated in MASLD-Related Cirrhosis

Saroglitazar is not recommended as a MASLD-targeted therapy in either compensated or decompensated cirrhosis according to current international guidelines, as it lacks large Phase III trials demonstrating histological improvement in liver fibrosis or steatohepatitis. 1

Guideline-Based Recommendations for MASLD with Cirrhosis

Compensated Cirrhosis (Child-Pugh A)

The 2024 EASL-EASD-EASO guidelines provide clear pharmacological options that do NOT include saroglitazar 2:

For Type 2 Diabetes:

• GLP-1 receptor agonists (semaglutide, liraglutide, dulaglutide) or dual GIP/GLP-1 agonists (tirzepatide) are the preferred first-line agents 2, 1
• SGLT2 inhibitors (empagliflozin, dapagliflozin) can be safely used in Child-Pugh class A cirrhosis 2, 3
• Metformin can be used if GFR >30 ml/min 2
• Insulin should be used if decompensation occurs 2

For Dyslipidemia:

• Statins should be used according to cardiovascular risk guidelines and are safe in compensated cirrhosis 2

Decompensated Cirrhosis (Child-Pugh B/C)

Insulin is the ONLY evidence-based treatment option for diabetes in decompensated cirrhosis 4:

Contraindicated medications:

• Metformin is absolutely contraindicated due to lactic acidosis risk, especially with renal impairment 2, 4
• Sulfonylureas must be avoided due to severe hypoglycemia risk 2, 4
• GLP-1 receptor agonists are contraindicated in Child-Pugh C cirrhosis and require caution in Child-Pugh B 1, 4
• SGLT2 inhibitors should not be used in decompensated cirrhosis 4

Why Saroglitazar is Not Recommended

Lack of Guideline Support

The European guidelines explicitly state that saroglitazar is not recommended as a MASLD-targeted therapy due to insufficient evidence from large Phase III trials 1. The 2024 EASL-EASD-EASO treatment algorithms for MASLD with cirrhosis do not include saroglitazar among preferred pharmacological options 2.

Limited Evidence Base

While observational studies suggest saroglitazar may be safe in compensated cirrhosis 5, 6, these are small, single-arm studies without the robust evidence required for guideline recommendations:

• A 2025 single-center study (n=26) showed improvements in liver enzymes and modest LSM reduction over 24 weeks, but only 15.3% showed clinically meaningful LSM regression ≥0.75 kPa 5
• A 2023 real-world study (n=63, including 11 with compensated cirrhosis) demonstrated improvements in biochemical parameters but lacked histological endpoints and long-term outcomes 6

Safety Concerns in Cirrhosis

No large-scale safety data exist for saroglitazar in decompensated cirrhosis, and the medication has not been studied in this population 5, 6.

Clinical Algorithm for MASLD with Cirrhosis

Step 1: Determine cirrhosis status

• Compensated (Child-Pugh A) vs. decompensated (Child-Pugh B/C)
• Check for clinically significant portal hypertension using LSM ≥20 kPa and/or platelet count <150×10⁹/l 2

Step 2: For compensated cirrhosis with diabetes:

• First-line: GLP-1 receptor agonists or GIP/GLP-1 co-agonists 2, 1
• Alternative: SGLT2 inhibitors 2, 3
• Consider: Metformin if GFR >30 ml/min 2

Step 3: For decompensated cirrhosis with diabetes:

• Use insulin ONLY, initiated in hospital setting due to glucose variability and hypoglycemia risk 4
• Discontinue all oral agents and GLP-1 receptor agonists 4

Step 4: Address cardiovascular risk:

• Continue statins for cardiovascular protection even in compensated cirrhosis 2

Step 5: Nutritional management:

• High-protein diet (1.2-1.5 g/kg/day) with late-evening snack for sarcopenia prevention 2
• Aim for ≥35 kcal/kg/day 2, 4

Off-Guideline Considerations

Saroglitazar may only be considered in highly specific contexts where guideline-recommended therapies are unavailable, unaffordable, or contraindicated, but this represents off-guideline use based solely on observational data 1. Patients must be counseled about the lack of robust evidence for liver-specific outcomes, and transition to guideline-recommended therapies should occur when feasible 1.

Critical Pitfalls to Avoid

• Do not use saroglitazar as a substitute for proven therapies (GLP-1 RAs, SGLT2 inhibitors) in compensated cirrhosis 2, 1
• Never use any oral agents or GLP-1 RAs in decompensated cirrhosis—insulin is the only safe option 4
• Do not continue metformin in decompensated cirrhosis due to lactic acidosis risk 2, 4
• Do not delay treatment waiting for liver biopsy in patients with high-risk noninvasive test results requiring diabetes management 1
• Monitor for increased infection risk in MASLD-cirrhosis compared to other etiologies 7