The life-threatening complications of type 2 diabetes constitute a significant unmet medical need worldwide, particularly because the prevalence of type 2 diabetes has soared in recent years as a result of changing eating habits and lifestyles. The current selection of antidiabetic drugs successfully manage the disease, but until the late 2005 release of results from the Prospective Pioglitazone Clinical Trial in Macrovascular Events (PROactive) study, no data quantified the effects of antidiabetic drugs on the incidence of cardiovascular disease (CVD). While the results of the PROactive study suggest that pioglitazone, a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist, may mitigate the occurrence of cardiovascular events in type 2 diabetes patients with a history of CVD, certain aspects of the PROactive study have been a cause for concern among members of the medical community. This report discusses the PROactive study, beginning with an overview of type 2 diabetes, including information on its increasing prevalence and associated comorbidities, particularly cardiovascular complications, and available therapies. Next, we discuss pioglitazone's pharmacological profile as well as the design, results, and possible shortcomings of this breakthrough trial. Finally, we forecast the potential effect of the PROactive study on sales of pioglitazone and the commercial opportunities for other antidiabetic agents.

Introduction: Promising Results in the Recent PROactive Study

Type 2 Diabetes: Disease Background and Prevalence