The need for outcome studies in type 2 diabetes

Abstract

Outcome studies use primary end points such as overall mortality or major morbidity to demonstrate that treatments deliver meaningful clinical benefits. Historically it was thought that most of the cardiovascular morbidity due to diabetes was related to microvascular disease, providing a marker for macrovascular disease. In diabetes an outcome study would measure all-cause death, cardiac death and cardiovascular morbidity (end points related to macrovascular disease), whereas conventional trials in diabetes have used surrogate end points, such as blood pressure, microvascular disease (retinopathy, nephropathy) or glycaemic control, which may not predict clinical benefits in the prevention of macrovascular end points. Although outcome trials are increasingly required by regulatory or funding agencies, few have been performed in diabetes; most data have come from trials with surrogate end points or subgroup analyses of cardiovascular outcome trials. Methodological constraints, particularly the large patient populations and long follow-up required, partly explain the lack of outcome studies in diabetes.

The PROspective pioglitAzone Clinical Trial In macroVascular Events (PROactive) is a macrovascular outcome study in patients with type 2 diabetes. It will involve approximately 4,000 patients who will receive pioglitazone or placebo in addition to their existing therapy. Principal end points will be all-cause mortality and severe disability due to macrovascular complications. PROactive should provide important data on the impact of therapy on the incidence of cardiovascular complications in type 2 diabetes.