Effects of thiazolidinediones on the triad of type 2 diabetes mellitus, insulin resistance and cardiovascular disease

Type 2 diabetes is associated with an increased risk of cardiovascular events that carry a poor prognosis. Majority of patients with type 2 diabetes are insulin resistant and have associated metabolic abnormalities that are also significant cardiovascular risk factors. Thiazolidinediones (TZDs) are currently the only available oral anti-hyperglycaemic medications that reduce insulin resistance. In addition to lowering blood glucose, TZDs have been shown to affect and reduce surrogate markers of CV risk in patients with type 2 diabetes. PROactive was the first prospective randomized, double-blind, placebo-controlled outcome study on high risk type 2 diabetes patients using pioglitazone. Although the primary endpoint of the PROactive study was not reached, the results of the secondary endpoints are consistent with an anti-atherosclerotic effect of the medication. Ongoing TZD clinical trials should provide additional information or definitive evidence as to whether TZDs can reduce CV risk. Current emphasis should be placed on reducing CV risk factors and improving glycaemic control, when possible, and the clinician should be alert for signs and symptoms of atherosclerosis.