Implications of Rosiglitazone and Pioglitazone on Cardiovascular Risk in Patients With Type 2 Diabetes Mellitus

Brian K. Irons, PharmD; Ronald Shane Greene, PharmD; Timothy A. Mazzolini, PharmD; Krystal L. Edwards, PharmD; Rebecca B. Sleeper, PharmD


Pharmacotherapy. 2006;26(2):168-181. 

In This Article

Abstract and Introduction


Clinical data suggest that thiazolidinediones-specifically, rosiglitazone and pioglitazone-may improve cardiovascular risk factors through multiple mechanisms. Low insulin sensitivity has been described as an independent risk factor for coronary artery disease and cerebrovascular disease. Patients with insulin resistance often have several known risk factors, such as obesity, dyslipidemia, and hypertension. Other emerging risk factors may be prevalent in patients with insulin resistance, such as hyperinsulinemia, elevated C-reactive protein, elevated plasminogen activator inhibitor levels, and small, dense, low-density lipoproteins. The only available drug class that primarily targets insulin resistance is the thiazolidinediones. These drugs have shown efficacy in affecting surrogate markers of cardiovascular risk in patients with diabetes mellitus. Alterations in these risk factors are likely due to their effects on improving insulin sensitivity and/or glycemic control. Trials to assess whether thiazolidinediones actually reduce cardiovascular outcomes are continuing.


Patients with type 2 diabetes mellitus have a significantly higher risk for cardiovascular disease than those without diabetes. The risk of a cardiovascular event or death in a patient with diabetes is similar to that in a patient with existing heart disease and no diabetes.[1] Type 2 diabetes is considered the sixth leading cause of death in the United States, with most of these deaths attributed to cardiovascular disease.[2,3] With respect to treatment costs, more of the direct costs are for treating the cardiovascular complications of diabetes than for any other complication.[4] With a 2–4-fold higher risk of heart disease or cerebrovascular disease and the increasing prevalence of diabetes in the United States, the toll of diabetes-related heart disease in the decades to come is nothing less than alarming.[3,5]

Increasing clinical data suggest that thiazolidinediones may reduce cardiovascular risk factors through multiple mechanisms.[6–10] Much of the literature supporting this potential new role of thiazolidinediones is centered around troglitazone, which was taken off the U.S. market several years ago secondary to the risk of hepatotoxicity. Thus, this review focuses specifically on the human data connecting cardiovascular risk reduction and the currently available thiazolidinediones in the United States, rosiglitazone and pioglitazone.


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