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BACKGROUND Diabetes (T2DM) is a worldwide medical and social emergency in the westernized societies. Lifestyle changes, diet and physical activity, have shown a protective effect on the likelihood of developing T2DM and are strongly recommended for primary prevention in people at increased risk for T2DM. However, maintaining adherence to these nonpharmacologic strategies is dishearteningly challenging, and the possible use of drugs to prevent T2DM remains of keen interest. Metformin, glitazones, acarbose and orlistat can reduce the risk of developing T2DM. Recently, post hoc analyses of several clinical studies suggested that ACE-I as well might reduce the risk of T2DM.  AIM OF THE STUDY Since none of these trials was designed with this primary end-point, the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) Investigators studied the effects of ramipril or rosiglitazone on the risk of T2DM in a randomized trial designed with T2DM as a primary outcome.  METHOD Subjects with fasting impaired plasma glucose levels or impaired glucose tolerance, without cardiovascular disease, were randomly assigned, in a 2-by-2 factorial design, to receive either ramipril (up to 15 mg daily) or placebo and either rosiglitazone or placebo. They were followed for a median of 3 years.  RESULTS Rates of the primary end points, T2DM or death, were not significantly lower in the ramipril group than in the placebo group. In contrast to ramipril, the use of rosiglitazone resulted in a significant reduction in T2DM or death.  DISCUSSION Disappointingly, 14 participants on rosiglitazone developed non-fatal heart failure, compared with 2 cases in the placebo group, and the group gained 3% (2.2 kg) more in body weight than the placebo group. Moreover, we still do not know whether the effect of rosiglitazone on the incidence of T2DM will persist after drug washout.  CONCLUSIONS We believe that the high cost of the drug and the study’s negative cardiovascular and body weight outcomes favour a lifestyle strategy in preventing T2DM

Trial update: the Diabetes REduction Approaches with ramipril and rosiglitazone Medications (DREAM) trial