Saroglitazar: A Comprehensive Pharmacological and Clinical Monograph of a First-in-Class Dual PPAR Agonist

Executive Summary

Saroglitazar represents a significant innovation in the management of complex metabolic disorders, emerging as the first and only approved agent in the "glitazar" class. Its unique pharmacological profile is defined by its action as a dual agonist of Peroxisome Proliferator-Activated Receptors (PPARs), with a carefully engineered balance of predominant PPAR-α and moderate PPAR-γ activity. This molecular design successfully uncouples potent therapeutic effects on lipid and glucose metabolism from the class-limiting adverse effects that led to the failure of previous dual agonists.

Clinically, Saroglitazar has established robust efficacy in its approved indications in India: diabetic dyslipidemia and Non-Alcoholic Fatty Liver Disease (NAFLD) / Non-Alcoholic Steatohepatitis (NASH). In diabetic dyslipidemia, head-to-head trials have demonstrated its superiority over the thiazolidinedione pioglitazone in improving atherogenic lipid profiles while maintaining comparable glycemic control. In NAFLD/NASH, clinical data from the EVIDENCES trial program has shown significant improvements in liver enzymes, hepatic fat content, and underlying metabolic drivers, positioning it as a promising disease-modifying therapy in a field with no approved treatments.

The drug's safety profile is a key differentiator. It is notably devoid of the weight gain and peripheral edema associated with potent PPAR-γ agonists and has shown a more favorable renal and hepatic safety profile compared to fibrates. While a mild increase in serum creatinine has been noted in some analyses, its non-renal route of excretion is a significant advantage for patients with comorbid diabetic nephropathy.