Chiglitazar, a PPAR pan-agonist: Impacts on type 2 diabetes mellitus and multi-system metabolic regulation – A review

Type 2 diabetes mellitus (T2DM) is a prevalent chronic metabolic disorder with multifactorial pathogenesis involving genetic predisposition, environmental influences, and dietary habits. Insulin resistance represents a central pathophysiological mechanism. Current evidence suggests that peroxisome proliferator-activated receptors (PPARs)-including PPARα, PPARδ, and PPARγ-can effectively ameliorate insulin resistance and associated metabolic syndromes; however, overstimulation of a single receptor subtype may lead to adverse effects. As a novel pan-PPAR agonist, chiglitazar achieves balanced activation of all three PPAR subtypes, providing significant glycemic control while exhibiting potential therapeutic benefits for metabolic-associated steatohepatitis (MASH), dyslipidemia, and other metabolism-related systemic disorders, thereby demonstrating superior metabolic regulatory properties. This review examines the interplay between T2DM and PPARs, explores the pharmacological mechanisms, clinical efficacy, and safety profile of chiglitazar, and highlights its multi-system metabolic benefits beyond glycemic control. These findings provide theoretical and practical insights supporting its clinical application in T2DM and related metabolic disorders.