Commentary: Of hopes and DREAMS: The quest to prevent type 2 diabetes

University of Washington Seattle, Seattle, Washington, United States
Journal of Clinical Endocrinology &amp Metabolism (Impact Factor: 6.21). 01/2007; 91(12):4762-3. DOI: 10.1210/jc.2006-2164
Source: PubMed


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 Dia- betes Prevention Program clearly demonstrated that inten- sive 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 Preven- tion Study reported similar findings (2). One would think that therein lies the simple answer to diabetes prevention. Unfortunately,translationoftheseresultstothegeneralpub- lic has been difficult. Large, randomized trials have also assessed the potential of the medications metformin (Dia- betes Prevention Program) and acarbose (STOP-NIDDM) to slow the progression to diabetes, and these have both dem- onstrated some benefit (1, 3). When one compares the results in the Diabetes Prevention Program, metformin was only abouthalfaseffectiveaswasintensivelifestylechange.Acar- bose, 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 com- panies and clinical trialists continue to investigate the effect of pharmacological therapy to prevent diabetes. The most recent large clinical trial to address the preven- tion 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 renin- angiotensinsystemdecreasesincidentdiabetes.Inparticular, the HOPE study demonstrated a significant reduction in new-onset diabetes in people with increased cardiovascular risks (6). Second, rosiglitazone is a thiazolidinedione insulin- sensitizer, 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 glucose- lowering effect, the drug did not slow the rate of develop- ment of diabetes. In contrast, rosiglitazone (titrated to 8 mg/d) very significantly reduced the development of dia- betes by some 60% in this relatively healthy population with impaired fasting glucose or impaired glucose tolerance.

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    ABSTRACT: The prevention of type 2 diabetes mellitus (DM2) is a major health issue. The DREAM trial is a multinational, multicentre, prospective double-blind study of 5269 patients with an increased risk of developing diabetes. The results show that treatment with rosiglitazone reduces the risk of developing diabetes in this relatively healthy population. The success is achieved at the expense of side effects such as increased weight gain and a higher incidence of non-fatal congestive heart failure. The DREAM trial provides interesting data that may have major implications, but at the same time raises a number of questions that need to be addressed. The ADOPT study shows the benefits of rosiglitazone over glyburide in de novo DM2.
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