PPARγ agonists—Antidiabetic drugs with a potential role in the treatment of diseases other than diabetes

The use of thiazolidinediones (TZDs) for treating patients with type 2 diabetes mellitus (T2DM) has been expansively increasing. Although troglitazone was withdrawn from the market, rosiglitazone and pioglitazone are currently available in several countries worldwide. Insulin resistance is one of the major pathophysiological alterations in T2DM and can be decreased by using TZDs. TZDs can be used in combination with other oral antidiabetic drugs, preferably with metformin or sulfonylureas. The effects of TZDs are explained by their peroxisome proliferator activator receptor-γ (PPARγ) activating characteristics. Activation of PPARγ leads to lowering blood glucose in diabetic patients but this mechanism may also result in prevention of T2DM. TZDs due to their specific PPARγ activation can be used for reducing cardiovascular risk and even for decreasing certain cardiovascular events. In addition, TZDs are considered promising for the treatment of patients with clinical conditions other than diabetes. Some of the benefits of TZDs have been documented by randomised controlled clinical trials while others are still to be proven. TZDs have well characterised side effects, therefore the benefit–risk ratio should carefully be evaluated.