Routine blood pressure lowering and intensive glucose control in patients with Type 2 diabetes: the ADVANCE trial

The Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial investigated the effects of routine blood pressure lowering and intensive blood glucose control on major vascular events in people with Type 2 diabetes. In this factorial randomized study, 11,140 individuals with Type 2 diabetes were randomly assigned to a fixed combination of perindopril and indapamide or matching placebo, and to intensive glucose control with the use of modified-release gliclazide plus other drugs required to achieve a hemoglobin A1c of 6.5% of less, or standard guideline-based glucose control. The primary outcomes were composites of major macrovascular and major microvascular events (major vascular events), analyzed jointly and separately. Active treatment in the blood pressure-lowering arm reduced blood pressure by 5.6/2.2 mmHg compared with placebo, and the relative risks of major vascular events, all deaths and cardiovascular deaths by 9% (p = 0.043), 14% (p = 0.025) and 18% (p = 0.027), respectively. These effects appeared independent of the initial blood pressure level or the use of concomitant treatments. Intensive glucose control lowered glycated hemoglobin levels to a mean of 6.5% and reduced the relative risk of major vascular events by 10% (p = 0.01), primarily through a 21% (p = 0.006) reduction in nephropathy. Intensive glucose control was not associated with a significant reduction in macrovascular events; however, unlike reports from the recently reported Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, there was no evidence of any increase in all-cause mortality or cardiovascular death with more intensive glucose control. This trial has provided important new evidence with direct implications for clinical management of blood pressure and blood glucose in patients with Type 2 diabetes.