Improving the prognosis in patients with diabetes: What will ADVANCE tell us?

The rising tide of diabetes fueled by an epidemic of obesity is worrisome, particularly in view of the anticipated increase in cardiovascular morbidity and mortality associated with such changes in the future. There is an urgent need to offset this predicted rise in cardiovascular events by improving the current understanding of the importance of the independent and net benefits of glycemic and blood-pressure control, and the use of multirisk interventions in patients with diabetes. Current knowledge about the benefits of various interventions is reviewed: glycemic control, blood pressure-lowering, lipid lowering, and others. Also, some of the unresolved questions relating to the optimal management of Type 2 diabetes are identified. The extent to which results of the ADVANCE trial (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release (MR) Controlled Evaluation) will answer some of these questions is considered. ADVANCE is a large, multicenter, randomized controlled trial, and uses a factorial 2 x 2 design to determine the effects on macrovascular and microvascular outcomes of blood pressure-lowering (using an angiotensin-converting enzyme inhibitor and diuretic combination) and of intensive glucose control using a gliclazide MR-based regimen. 11,140 patients were randomized, and followed for 5.5 years for two primary outcomes: (1) a composite of nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death, and (2) new or worsening nephropathy or microvascular eye disease. The ADVANCE trial is likely to provide generalizable data on the benefits of blood pressure-lowering, regardless of initial blood pressure and intensive glucose control beyond current glycemic targets, and may resolve current issues about the net benefits of the two interventions. (c) 2007 American Journal of Hypertension, Ltd.