Saroglitazar in NAFLD
Do Not Use Saroglitazar for NAFLD Treatment
Saroglitazar is not recommended for treating NAFLD, as it lacks regulatory approval for this indication and is not mentioned in any major clinical practice guidelines from the American Association for the Study of Liver Diseases, American Gastroenterological Association, or European Association for the Study of the Liver. 1, 2, 3
Why Guidelines Do Not Recommend Saroglitazar
Established PPAR-γ Agonist Recommendations
Pioglitazone (not saroglitazar) is the only thiazolidinedione with guideline support for NAFLD, specifically for patients with biopsy-proven NASH and fibrosis at 30-45 mg daily. 1, 2, 4
Pioglitazone has demonstrated histological improvement in multiple randomized controlled trials, including resolution of NASH in 51% of patients and improvement in fibrosis (p=0.039) in an 18-month study of 101 patients with biopsy-proven NASH. 1
The American Association for the Study of Liver Diseases explicitly states that pharmacological treatments should be restricted to patients with biopsy-proven NASH and fibrosis, as those without steatohepatitis or fibrosis have excellent prognosis from a hepatic standpoint. 2, 4
Limited Evidence for Saroglitazar
Saroglitazar research consists only of small observational studies (n=30-107 patients) with short follow-up periods (6-24 weeks) using surrogate endpoints like transaminases and FibroScan measurements rather than liver biopsy histology. 5, 6
These observational studies lack the randomized controlled design, adequate sample size, and histopathological endpoints required before guideline recommendations can be made. 1
The mechanistic review of saroglitazar describes theoretical PPAR-α/γ pathways but provides no clinical trial data demonstrating improved morbidity, mortality, or quality of life outcomes. 7
What to Use Instead
First-Line Therapy: Lifestyle Modification
Target 7-10% total body weight loss through Mediterranean diet and vigorous-intensity exercise (≥6 METs) for at least 150 minutes per week, as this magnitude of weight loss improves steatosis, inflammation, and potentially fibrosis. 2, 3
Implement caloric restriction of 500-1000 kcal/day deficit with gradual weight reduction not exceeding 0.5-1 kg per week. 1, 2, 3
Metabolic Comorbidity Management
For patients with type 2 diabetes and NAFLD, prescribe GLP-1 receptor agonists (liraglutide, semaglutide) or SGLT2 inhibitors as first-line therapy, as they improve cardiometabolic profile and reverse steatosis. 2, 3
Use statins to treat dyslipidemia according to cardiovascular risk, as they are safe in NAFLD patients, reduce HCC risk by 37%, and should not be withheld. 2, 3
Liver-Directed Pharmacotherapy (Only for Biopsy-Proven NASH with Fibrosis)
Consider vitamin E 800 IU daily in non-diabetic, non-cirrhotic patients with biopsy-proven NASH. 1, 2, 4
Consider pioglitazone 30 mg daily in patients with biopsy-proven NASH without cirrhosis, with or without diabetes, accepting the trade-off of 2.5-3.0 kg weight gain. 1, 2, 4
Critical Pitfalls to Avoid
Do not use metformin as specific treatment for NAFLD histology—despite metabolic benefits, it does not significantly improve liver histology in patients with NAFLD and NASH according to two published meta-analyses. 1, 4
Never pursue pharmacotherapy without first establishing disease severity through FIB-4 score or liver stiffness measurement, as low-risk patients (FIB-4 <1.3) require lifestyle modifications alone. 2, 3
Avoid using any PPAR-γ agonist in patients without biopsy confirmation of NASH and fibrosis, as the risk-benefit ratio does not favor treatment in those with simple steatosis. 2, 4