DREAM trial: Ramipril fails to reduce the incidence of new-onset diabetes or death

In a randomized, double-blind, placebo-controlled trial, the angiotensin-converting enzyme (ACE) inhibitor ramipril, when administered to patients with prediabetes but no previous cardiovascular disease, failed to demonstrate a statistically significant reduction in the primary composite end point of new-onset diabetes or death.

These results from the Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication (DREAM) trial-the first trial specifically designed to determine whether an ACE inhibitor could prevent diabetes-were recently published in The New England Journal of Medicine (NEJM).

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 randomized in a 2×2 factorial fashion to receive ramipril ≤15 mg/d (n=2,623) or matching placebo (n=2,646) (and rosiglitazone or placebo).

In 2 previous meta-analyses of randomized, controlled trials published in the journals Diabetes Care and the Journal of the American College of Cardiology, ACE inhibitors demonstrated an ability to significantly reduce the development of new-onset diabetes by 21% to 27%. The authors of the DREAM trial suggested a number of potential reasons as to why these previous results may differ from their new data, including their trial participants' lack of pre-existing cardiovascular disease at randomization, their trial's comparison of ramipril with placebo instead of with another blood pressure-lowering agent such as a diuretic or a beta blocker-agents that may actually increase a patient's risk of diabetes-and finally, their trial's shorter duration of patient follow-up compared with previous trials.

Based on these new data and the currently available literature, the authors cautioned, "For now, routine use of ramipril for the express purpose of preventing diabetes is not indicated," but they did suggest that additional research should be conducted to clarify an ACE inhibitor's role in the prevention of diabetes.

Currently, for the 41 million people in the United States who are aged 40 to 74 years and have prediabetes, lifestyle modifications, including weight loss and increased physical activity, are still the best strategies for preventing diabetes, according to the authors and the American Diabetes Association (ADA).

SOURCES The Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication (DREAM) Trial Investigators. Effect of ramipril on the incidence of diabetes. N Engl J Med. 2006;355:1551–1562.

Gillespie EL, White CM, Kardas M, Lindberg M, Coleman CI. The impact of ACE inhibitors or angiotensin II type 1 receptor blockers on the development of new-onset type 2 diabetes. Diabetes Care. 2005;28:2261–2266.

Abuissa H, Jones PG, Marso SP, O'Keefe JH Jr. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for prevention of type 2 diabetes: A meta-analysis of randomized clinical trials. J Am Coll Cardiol. 2005;46:821–826.

American Diabetes Association and National Institute of Diabetes, Digestive and Kidney Diseases. The prevention or delay of type 2 diabetes. Diabetes Care. 2002;25:742–749.

American Diabetes Association. Pre-diabetes. Available at: http:// http://www.diabetes.org/diabetes-prevention/pre-diabetes.jsp. Accessed November 1, 2006.