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

The DREAM Trial Investigators (2006) Effect of ramipril on the incidence of diabetes. N Engl J Med 355: 1551–1562

An international team of investigators has evaluated the effects of rosiglitazone, an antihyperglycemic drug, and ramipril, an angiotensin-converting-enzyme inhibitor, on the development of diabetes in a double-blind, placebo-controlled, randomized, multicenter trial. Results for each drug were reported separately.

In total, 5,269 participants (mean age 54.7 years) who had impaired fasting plasma glucose levels or impaired glucose tolerance were randomly assigned to receive placebo, rosiglitazone or ramipril monotherapy, or both drugs. Participants were followed up for a median of 3 years.

During the trial, diabetes development or death occurred in markedly fewer patients in the rosiglitazone-treated group (11.6%) than in the placebo-treated group (26%). Rosiglitazone treatment reduced both the median fasting plasma glucose level and the 2 h postchallenge plasma glucose concentration, and increased the likelihood of returning to normoglycemia by about 70–80% as compared with placebo treatment. A possible adverse effect of rosiglitazone might be the increased occurrence of nonfatal congestive heart failure (0.5% in rosiglitazone-treated patients versus 0.1% placebo-treated patients), but there were no major differences between the two groups in the incidence of other cardiovascular events.

Compared with placebo, ramipril did not substantially reduce the incidence of diabetes development or death, but it did increase the rate of regression to normoglycemia (by 16%). In ramipril-treated patients, 2 h postchallenge plasma glucose levels were slightly lower than in placebo-treated patients.

The authors suggest that rosiglitazone could be used to treat dysglycemia and might prevent the onset of diabetes in high-risk individuals. Ramipril apparently has favorable effects on glucose metabolism, but extended follow-up might be required to detect any effect on diabetes development. The authors conclude that, at present, ramipril cannot be recommended for diabetes prevention.