Advances in antidiabetic agents targeting peroxisome proliferator-activated receptors (PPARs)

Abstract

One of the most promising approaches for the discovery of new antidiabetic agents is represented by the exploitation of peroxisome proliferator-activated receptor (PPAR) ligands. New agents that selectively target PPARs and molecules with combined activity on several PPARs (i.e., PPARa and PPARy) have been identified as potentially superior therapeutic agents for metabolic diseases. These include: 1) PPARa agonists, which exert significant antidyslipidemic and antiatherosclerotic effects; 2) PPARy agonists, which are effective in treating type 2 diabetes; 3) selective partial PPARy agonists with robust antidiabetic efficacy and fewer adverse effects than currently available agonists; 4) PPARy antagonists, which are powerful tools to study PPARy signaling pathways; 5) dual PPARa/y agonists, which beneficially affect carbohydrate and lipid metabolism; 6) PPARδ agonists, which may have beneficial effects on circulating lipids and obesity; and 7) pan-PPARaα/γ/δ agonists with excellent antidiabetic activity. The advances in antidiabetic agents targeting PPARs are summarized in this review.