A Comparative Evaluation of the Effects of Saroglitazar and Pioglitazone on Hepatic and Metabolic Parameters in Type 2 Diabetes Mellitus With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).

Background and objective Type 2 diabetes mellitus (T2DM) is frequently accompanied by metabolic dysfunction-associated steatotic liver disease (MASLD), compounding morbidity and mortality risks. Pharmacologic strategies that directly target hepatic steatosis and fibrosis in this population remain limited. Saroglitazar, a dual PPARα/γ agonist, and pioglitazone, a proliferator-activated receptor gamma (PPAR-γ) agonist, may offer potential benefits. This study aimed to compare their effects on hepatic, glycemic, and metabolic parameters in patients with T2DM and MASLD. Methods In this study, 96 adults with T2DM and MASLD were randomized to receive either pioglitazone 15 mg or saroglitazar 4 mg daily for 12 months. Primary outcomes included changes in the non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS), liver stiffness measurement (LSM), and controlled attenuation parameter (CAP). Secondary outcomes assessed fasting plasma glucose (FPG), postprandial glucose (PPPG), HbA1c, lipid profile, triglyceride-glucose (TyG) index, and BMI. Assessments were performed at baseline and at three, six, and 12 months. Data were analyzed using paired and unpaired t-tests. Results Saroglitazar produced a significant reduction in NFS (-0.57, p = 0.026) and a non-significant decrease in LSM (-1.1 kPa). CAP declined by 18.6 dB/m (p = 0.059). HbA1c dropped by 0.81% (p<0.0001) with saroglitazar, surpassing pioglitazone's 0.31% reduction. Both groups showed modest improvements in lipid levels and stable TyG indices. Saroglitazar led to a significant BMI reduction (-3.32 kg/m², p = 0.006); pioglitazone showed no BMI change. Both treatments were well tolerated, with no major adverse events reported. Conclusions Saroglitazar demonstrated superior benefits over pioglitazone in improving hepatic steatosis and fibrosis, glycemic control, and BMI in patients with T2DM and MASLD, while maintaining a favorable safety profile.