Type 2 diabetes mellitus affects about 5 percent of adults and has rapidly rising prevalence that is a significant concern. Persons with impaired glucose tolerance are at high risk of progression to type 2 diabetes and substantial morbidity and mortality. Lifestyle interventions such as diet and physical activity modification can reduce progression to diabetes in persons with impaired glucose tolerance by about one half, but these require significant commitment. Medications such as metformin (Glucophage) and acarbose (Precose) can reduce progression by about 25 to 30 percent. The DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication) study was designed to assess the ability of rosiglitazone (Avandia) to reduce progression to diabetes in persons with impaired glucose tolerance or elevated fasting blood glucose levels.
The DREAM Trial Investigators identified more than 24,000 persons 30 years and older with impaired glucose tolerance or elevated fasting blood glucose levels at 191 sites in 21 countries. Exclusion factors included personal history of diabetes, cardiovascular disease, or intolerance to the study medications. Participants who demonstrated the ability to adhere to medication regimens during a 17-day run-in period were eligible for randomization.
In the study 2,635 patients were randomly selected to receive rosiglitazone (4 mg daily for two months then 8 mg daily), and 2,634 received an identical placebo. Participants were assessed after two and six months and then every six months for a median follow-up of three years. The assessment visits included advice on diet and lifestyle and evaluation of adherence and adverse effects from the medications. Fasting blood glucose and glycated hemoglobin concentrations were measured annually. A 75-g oral glucose tolerance test was performed after two years and at the final study visit. Other data included weight, waist and hip circumference, blood pressure, electrocardiography, and alanine transferase concentration. The primary end point was incident diabetes or death from any cause. Secondary outcomes included regression to normal fasting and two-hour postload blood glucose concentrations, cardiovascular event (e.g., myocardial infarction, stroke, heart failure, revascularization procedure, evidence of ischemia), and renal outcomes suggesting microvascular damage.
Of the 5,204 persons for whom adherence could be verified, 1,868 (71.7 percent) of the rosiglitazone group and 1,952 (75.1 percent) of the placebo group were at least 80 percent compliant with study medications. Overall, 938 (17.8 percent) participants progressed to diabetes and 63 (1.2 percent) died. The primary outcome of diabetes or death occurred in significantly fewer persons in the rosiglitazone group than the placebo group (11.6 versus 26 percent). The death rate was similar in the two groups. The beneficial effect of rosiglitazone was demonstrated in all age and ethnic groups, in both sexes, and in all types of baseline glucose abnormalities. The reduction in risk of diabetes was greatest in participants with the highest body mass indexes. The percentage of participants who became normoglycemic was significantly greater in the rosiglitazone group than in the placebo group (50.5 versus 30.3 percent). The median fasting plasma glucose concentration also was significantly lower in the rosiglitazone group. Mean body weight increased significantly more in the rosiglitazone group, but waist-to-hip ratio significantly decreased.
The authors conclude that rosiglitazone, with monitoring and lifestyle advice, substantially reduces the risk of type 2 diabetes in at-risk persons. They estimate the number needed to treat is seven over three years. These findings indicate that rosiglitazone is more effective than metformin and acarbose and may be more acceptable to patients. The reductions achieved with rosiglitazone are similar to those achieved with lifestyle modification. Because more than 8 percent of adults have impaired glucose tolerance or impaired fasting blood glucose, and up to 10 percent of these persons develop diabetes every year, the potential benefits of rosiglitazone and lifestyle modification are substantial.