DREAM trial: Rosiglitazone reduces the incidence of new-onset diabetes

In a randomized, double-blind, placebo-controlled trial recently published in Lancet, the thiazolidinedione (or "glitazone") rosiglitazone statistically significantly reduced the incidence of new-onset diabetes when given to patients diagnosed with prediabetes but lacking a prior history of cardiovascular disease. The benefits of using thiazolidinediones in the treatment of patients with diabetes are well known, but the current finding that thiazolidinediones can prevent prediabetics from progressing to diabetes is novel.

This was 1 of 2 recently published articles reporting results from the Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication (DREAM) trial. The other, published in The New England Journal of Medicine (NEJM), reported the failure of ramipril-an angiotensin-converting enzyme (ACE) inhibitor-to reduce a patient's risk of developing new-onset diabetes.

A total of 5,269 participants aged ≥30 years with impaired fasting glucose (>110 mg/dL but <126 mg/dL), impaired glucose tolerance (>140 mg/dL but <200 mg/dL when measured 2 hours after an oral glucose load), or both were recruited from 21 different countries and randomized in a 2×2 factorial fashion to receive rosiglitazone 8 mg per day (n=2,365) or matching placebo (n=2,634) (plus ramipril ≤15 mg/d or placebo). The primary end point of this analysis was the composite incidence of new-onset diabetes or death.

Participants receiving rosiglitazone also were more likely to regress to normoglycemia than those receiving placebo (HR=1.71; 95% CI, 1.57–1.87; P<.0001). The authors stated that "the reduction in diabetes reported here is of much the same magnitude as the reduction achieved with lifestyle approaches and greater than the reduction reported previously with drugs such as metformin or acarbose."

Not all of the results from the rosiglitazone arm of the DREAM trial were positive. Participants receiving rosiglitazone were >7 times more likely to be newly diagnosed with congestive heart failure compared with those receiving placebo (HR=7.03; 95% CI, 1.60–30.9; P=.01).

Although a significant increase in the development of heart failure was observed, the authors remarked that because of the small number of heart failure cases (n=16) in the trial as a whole, this finding requires cautious interpretation, as well as further analyses of these data and data from other thiazolidinedione studies to identify at-risk patients. To put the increased risk of heart failure into perspective, the authors stated, "Balancing both the benefits and risks suggests that for every 1,000 people treated with rosiglitazone for 3 years, about 144 cases of diabetes will be prevented, with an excess of 4 to 5 cases of congestive heart failure."

Currently, it is estimated that 41 million people in the United States and more than 8% of adults worldwide have prediabetes. For these patients, the authors referred to rosiglitazone as "a novel preventative approach that could be as, or more, effective and sustained than previously reported lifestyle approaches alone."

SOURCE The Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication (DREAM) Trial Investigators. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet. 2006;368:1096–1105.