Cardiovascular implications of thiazolidinedione therapy

The incidence of obesity and type 2 diabetes mellitus (DM2) in the United States has been increasing dramatically over the past 15 years, and is now at epidemic proportions. DM2 is the clinical manifestation of a long-term metabolic process that is initiated by cells' decreased sensitivity to the actions of insulin. Many outcome studies have identified DM2 as a strong and independent risk factor for the development of cardiovascular complications such as hypertension, arteriosclerosis, and heart failure. The goals of therapy in treating DM2 are to improve the long-term outlook for these patients. However, in selecting a therapeutic regimen for patients, clinicians should be aware that potentially severe adverse events may occur at a rate not previously identified in phase 3 studies. Certain therapies used to treat DM2, by effectively increasing the sensitivity of insulin, have also been reported to cause adverse effects, which can precipitate symptomatic heart failure. The purpose of this column is to discuss the therapeutic options available for treating patients with DM2, the potential pathophysiology of the adverse events of symptomatic heart failure, encouragement of use of the US Food and Drug Administration MedWatch program for reporting adverse events associated with medication therapy, and review of newer treatment guidelines for use of insulin-sensitizing agents in patients with chronic heart failure.