Pioglitazone was effective in improving insulin sensitivity and steatosis, while silymarin exhibited hepatoprotective effects but with relatively modest improvements.<h4>Interpretation and conclusions</h4> Saroglitazar demonstrated the most comprehensive protective effects against NAFLD progression, surpassing pioglitazone and silymarin in biochemical, histological, and insulin resistance parameters. This evidence concerns the gene INS and metabolic dysfunction-associated steatotic liver disease.