Diabetes Reduction Assessment With Ramipril and Rosiglitazone Medication - DREAM - Ramipril


The goal of the trial was to evaluate treatment with ramipril compared with placebo among patients without cardiovascular disease or a history of diabetes but with impaired glucose.

Study Design

Study Design:

Patients Screened: 24,592
Patients Enrolled: 5,269
Mean Follow Up: Median 3 years
Mean Patient Age: Mean age 55 years
Female: 59

Patient Populations:

Age ≥30 years; impaired fasting plasma glucose levels (110 - <126 mg/dl) or impaired glucose tolerance (140 - <200 mg/dl 2 hours after an oral glucose load) but without a history of diabetes, cardiovascular disease, or intolerance of either angiotensin-converting enzyme inhibitors or thiazolidinediones

Primary Endpoints:

Newly diagnosed diabetes or death

Secondary Endpoints:

Composite of cardiac and renal events, defined as myocardial infarction, stroke, cardiovascular death, revascularization, heart failure, newly diagnosed angina with objective evidence of ischemia, or ventricular arrhythmia requiring resuscitation or renal event based on urine and blood analysis; glucose levels

Drug/Procedures Used:

Following a 17-day placebo run-in phase, patients were randomized in a double-blind manner to ramipril (up to 15 mg/d) (n = 2,623) or placebo (n = 2,646). An oral glucose tolerance test was performed at 2 years and at final study visit.

In a 2 x 2 factorial design, patients were also randomized to rosiglitazone (n = 2,635) or placebo (n = 2,634).

Principal Findings:

Medication compliance at 2 years was 81.3% in the ramipril group and 84.8% in the placebo group. Median fasting plasma glucose level at baseline was 106 mg/dl. Mean systolic blood pressure (SBP) at baseline was 136 mm Hg and mean diastolic blood pressure (DBP) was 83.4 mm Hg. SBP was reduced to a greater extent in the ramipril group compared with placebo (8.2 mm Hg vs. 3.9 mm Hg, p < 0.001).

The primary endpoint of death or new diabetes occurred in 18.1% of the ramipril group and 19.5% of the placebo group (hazard ratio [HR] 0.91, p = 0.15). Among the components of the composite, 1.2% of patients in each treatment group died, and diabetes was diagnosed in 17.1% of the ramipril group versus 18.5% of the placebo group (p = NS). There was no difference between treatment groups in cardiovascular events (2.6% for ramipril vs. 2.4% for placebo, HR 1.08, p = 0.68). Glucose levels returned to normal more frequently in the ramipril group (42.5% vs. 38.2%, HR 1.16, p = 0.001).

At final study visit, median fasting plasma glucose levels were 102.7 mg/dl in the ramipril group and 103.4 mg/dl in the placebo group (p = 0.07); post-load glucose levels were 135.1 mg/dl in the ramipril group and 140.5 mg/dl in the placebo group (p = 0.01).


Among patients without cardiovascular disease or a history of diabetes but with impaired glucose, treatment with ramipril was not associated with a difference in the primary endpoint of death or new diabetes compared with placebo at a median follow-up of 3 years.

Unlike the ramipril and placebo comparison, the rosiglitazone and placebo comparison in the trial did demonstrate a reduction in new diabetes or death. Rosiglitazone, unlike ramipril, was effective for diabetes prevention in patients without cardiovascular disease.

The lack of benefit with ramipril on diabetes prevention in patients without cardiovascular disease differs from what was observed in the HOPE trial, in which ramipril was associated with a reduction in diabetes in a population with prior cardiovascular disease. However, it should be noted that in the HOPE trial, diabetes was not a prespecified endpoint, and it was self-reported rather than evaluated with glucose testing, as was done in the present study.


The DREAM Trial Investigators. Effect of Ramipril on the Incidence of Diabetes. N Engl J Med 2006 Sept 15;355:1551-62.

Clinical Topics: Heart Failure and Cardiomyopathies, Prevention, Diet

Keywords: Follow-Up Studies, Blood Pressure, Ramipril, Systole, Medication Adherence, Glucose Intolerance, Glucose Tolerance Test, Hypoglycemic Agents, Diastole, Thiazolidinediones, Diabetes Mellitus, Fasting

< Back to Listings