What's Next for Diabetes Prevention?

R ecent estimates of the prevalence of diabetes and prediabetes underscore that no community is being spared from this ever-advancing, non-communicable disease (1). Given that many individuals with these conditions are going to experience the long-term, ravaging outcomes of hyperglycemia, there is a continued and pressing need to develop approaches that will prevent the development and progression of diabetes as well as its micro-and macro-vascular complications. The last two decades have witnessed the introduction of a number of new classes of medications to treat diabetes and the refinement of others. We have also learned the benefits of more aggressive glucose lowering so that today interventions are frequently commenced earlier, and many patients are rapidly placed on more than a single agent. The focus on earlier intervention has also grown out of the recognition that the glucose elevation characterizing type 2 diabetes does not occur suddenly, but rather is a slow and progressive process with the pathophysiology well established at a time when the glucose levels have not yet reached the diagnostic thresholds (2). Thus, impaired glucose metabolism and diabetes represent a continuum and both are amenable to therapy. Intervening to prevent the development of diabetes has been a focus of a number of studies over the last decade. In these, both lifestyle modification and medications have been used and have, in general, been successful in delaying the onset of the disease. Lifestyle modification reduces the risk of developing diabetes by over 50% (3,4), with different classes of medications having more variable impact (4–8). The greatest benefit from pharmacological intervention occurs with the thiazolidinediones (6–8), which have been shown to be as good, if not better, than lifestyle intervention. In this issue of Diabetes Care, Retnakaran et al. (9) provide additional information about the effectiveness of pharmacologic intervention to prevent progression to diabetes from the Canadian Normoglycemia Outcome Evaluation (CANOE) Trial. The CANOE investigators treated individuals with impaired glucose tolerance with a low-dose combination of metformin and the thiazolidinedione rosiglitazone and demonstrated a reduction in the risk of developing diabetes (10), similar in magnitude to that seen with larger doses of thiazolidinedione monotherapy. The current report provides further information on glucose levels, insulin sensitivity, and b-cell function over the course of the study. As expected, glucose levels fell with combination therapy, the nadir being reached at 12 months, but thereafter they increased at a rate equivalent to that in the placebo …