Comparative Efficacy Of Remogliflozin, Telmisartan And Saroglitazar In An Experimental Rat Model Of Non-Alcoholic Fatty Liver Disease

Background: Non-alcoholic fatty liver disease (NAFLD) is a prevalent hepatic disorder associated with obesity, insulin resistance, and type 2 diabetes mellitus, with potential progression to non-alcoholic steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Despite its growing burden, pharmacological therapies remain limited. Saroglitazar, a dual PPAR-α/γ agonist, is approved in India for NAFLD, while remogliflozin, a selective SGLT2 inhibitor, and telmisartan, an angiotensin receptor blocker with partial PPAR-γ agonist activity, have demonstrated hepatoprotective potential in experimental studies. Aim: To evaluate the efficacy of remogliflozin, telmisartan in comparison with saroglitazar in improving biochemical and histopathological changes in high-fat diet-induced NAFLD in rats. Methods: Forty Sprague dawley rats were divided into normal control and high-fat diet groups. After 8 weeks of induction, NAFLD was confirmed histologically and biochemically in a subset. Remaining rats were allocated into untreated control, saroglitazar, remogliflozin, and telmisartan groups and treatment given for 6 weeks. Serum biochemical markers (AST, ALT, triglycerides) and histopathological evaluation (Sudan III and H&E staining) were performed to assess treatment efficacy. Results: High-fat diet feeding led to significant increases in body weight, liver enzymes, and triglycerides, with histological evidence of grade 2–3 steatosis and inflammation. Saroglitazar produced the most pronounced improvements in both biochemical parameters and liver histology, reversing steatosis to grade 0–1. Remogliflozin significantly reduced hepatic fat accumulation and improved liver enzymes, though mild residual steatosis persisted. Telmisartan demonstrated greater histological benefit than remogliflozin, with marked reduction in steatosis and inflammation, but its biochemical effects were less robust. Conclusion: Saroglitazar showed the most comprehensive efficacy, while remogliflozin and telmisartan also exerted hepatoprotective effects. Remogliflozin primarily improved biochemical markers, whereas telmisartan offered superior histological protection. These findings highlight their therapeutic promise in NAFLD and support further translational and clinical evaluation