Clinical Implications of the DREAM Study

Abstract

In response to an article (1) published in 2003 demonstrating that both diet and exercise as well as pioglitazone reduced insulin resistance in upper-body obese, sedentary, nondiabetic individuals, I wrote an editorial (2) discussing whether the treatment of insulin resistance independent of any effect on glycemia could be beneficial for reducing the risk of cardiovascular disease (CVD). At that time, evidence for a beneficial effect rested on surrogate end points and intermediate outcomes of CVD. The final sentence in the editorial was, “If the ongoing clinical trials demonstrate a reduction in hard clinical events, difficult decisions will need to be made.” Although thiazolidinediones (TZDs) continued to lower many of the surrogate risk factors associated with and early manifestations of CVD (e.g., endothelial dysfunction, intima medial thickness of carotid arteries) in subsequent studies, the effect on preventing hard clinical outcomes in the first clinical trial reported was less robust than many had anticipated (3). Now the Diabetes Reduction Assessment with Rampipril and Rosiglitazone Medication (DREAM) study (4) has been published, raising the question of treating nondiabetic individuals with a TZD, to reduce the risk of developing type 2 diabetes rather than CVD. The DREAM study (4) randomized over 5,000 individuals with impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG) to receive either 8 mg rosiglitazone or placebo over a median of 3 years. There was an ∼60% less chance of those receiving the TZD to develop diabetes compared with those receiving the placebo. For every 1,000 subjects with IFG and/or IGT given rosiglitazone, 144 would be prevented from developing diabetes. There would be, however, four to five excess cases (i.e., over what would have occurred if a TZD had not been given) of heart failure. In addition to the small increase in heart failure, the cost of the TZD …