Pioglitazone belongs to thiozolidinediones (TZD) class of anti diabetic agents used either as monotherapy or in combination with metformin, sulfonylureas or insulin in treatment of diabetes mellitus. The pioglitazone increase insulin sensitivity by increasing glucose utilization in adipose tissue, muscle, and liver and also by decreasing glucose production.1 The exact mechanism as to how pioglitazone exerts its effect is not fully understood. It binds to one or more peroxisome proliferator-activated receptors (PPARs), which regulate gene expression.2 PPARs are part of the steroid and thyroid super family of nuclear receptors found mostly in adipose tissue, pancreatic beta-cells, vascular endothelium, and macrophages while PPAR-alpha is expressed mostly in liver, heart, skeletal muscle, and vascular walls. Read more. . .