The members of the PPARgamma agonists, such as the thiazolidinediones, act as insulin sensitizer and improve insulin resistance. Several clinical studies have evaluated the efficacy of PPARgamma agonists in the management of insulin resistance and type 2 diabetes mellitus (T2DM). They are believed to improve insulin resistance by stimulating differentiation of small adipocytes, normalizing serum adipocytokine profile, and protecting pancreatic beta cells. They also possess powerful anti-atherogenic potency through amelioration of lipid profile and their anti-inflammatory effects. The PROactive study demonstrated that pioglitazone protects against hard end-point of macrovascular events in T2DM patients with previous macrovascular disease. A number of studies have also proven the potency of PPARgamma agonists in the prevention of onset of T2DM.