Commentary: Of HOPEs and DREAMs: the quest to prevent type 2 diabetes.

The old adage that “prevention is better than cure” holds particularly well for a chronic disease like type 2 diabetes, withitsepidemicscaleandmultiplecripplingcomplications. Clearly, any intervention that can halt this epidemic safely and effectively will have huge public health implications. Several clinical trials have therefore attempted to address the question of preventing diabetes. Among these, the Diabetes Prevention Program clearly demonstrated that intensive lifestyle change was effective not only in decreasing the progression of impaired glucose tolerance to diabetes, but was also associated with significant improvement in other cardiovascular risk factors (1). The Finnish Diabetes Prevention Study reported similar findings (2). One would think that therein lies the simple answer to diabetes prevention. Unfortunately,translationoftheseresultstothegeneralpublic has been difficult. Large, randomized trials have also assessed the potential of the medications metformin (Diabetes Prevention Program) and acarbose (STOP-NIDDM) to slow the progression to diabetes, and these have both demonstrated some benefit (1, 3). When one compares the results in the Diabetes Prevention Program, metformin was only abouthalfaseffectiveaswasintensivelifestylechange.Acarbose, although not compared head-to-head with intensive lifestyle,appearstobenobetterthanmetformin.Atthistime, neither of these drugs is currently approved for diabetes prevention. Whether they ever will be approved is another question. With the availability of other classes of agents with different mechanisms of action, many pharmaceutical companies and clinical trialists continue to investigate the effect of pharmacological therapy to prevent diabetes. The most recent large clinical trial to address the prevention of diabetes has been the Diabetes Reduction Assessment with Ramipril and Rosiglitazone (DREAM) trial (4, 5), for which there was a good rationale. First, post hoc analyses of a variety of studies have shown that blockade of the reninangiotensinsystemdecreasesincidentdiabetes.Inparticular, the HOPE study demonstrated a significant reduction in new-onset diabetes in people with increased cardiovascular risks (6). Second, rosiglitazone is a thiazolidinedione insulinsensitizer, and a previous drug in this class, which is no longer available, had been shown to prevent diabetes in a small single-center study in Hispanic women with a history of gestational diabetes (7); the same was suggested in a discontinued arm in the Diabetes Prevention Program (8). The DREAM trial was an international effort performed in 5269 individuals (59% women) of whom 44% had a history of hypertension, 44% were current or former smokers, and 36% had dyslipidemia. The results of the study were mixed (4, 5), which for the most part was not unexpected. The effect of ramipril (titrated to 15 mg/d) on glucose metabolism was small. Although the study demonstrated a modest glucoselowering effect, the drug did not slow the rate of development of diabetes. In contrast, rosiglitazone (titrated to 8 mg/d) very significantly reduced the development of diabetes by some 60% in this relatively healthy population with impaired fasting glucose or impaired glucose tolerance.