ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation), a landmark, six-year trial has now closed the part of the study that aims to investigate the effect of Preterax, a blood pressure lowering agent containing a fixed -dose combination of the ACE inhibitor perindopril and the diuretic indapamide, on the risk of macro- and micro- vascular complications in patients with type 2 diabetes mellitus.

ADVANCE is the largest clinical trial ever performed in patients with type 2 diabetes, involving over 11,000 randomised patients worldwide, and will provide important information about the separate and joint effects of blood pressure lowering using Preterax, and intensive blood glucose lowering using a gliclazide-based (Diamicron MR) regimen, compared with standard care in a broad cross-section of high-risk individuals with type 2 diabetes.

The study was initiated and designed by investigators at The George Institute for International Health, and received funding from the National Health and Medical Research Council of Australia and from Servier, the makers of Preterax and Diamicron MR. “People with diabetes have a two to four-fold greater risk of experiencing a cardiovascular event compared with non-diabetics. However, despite this high risk, there is surprisingly little recent evidence from randomised clinical trials on the role of blood pressure lowering in the prevention of diabetic vascular disease”, points out the ADVANCE study chairman John Chalmers from The George Institute. “ADVANCE will provide new evidence about the effects of blood pressure lowering and glucose lowering which could have huge implications for the practical management of type 2 diabetes.” 

Diabetes mellitus is emerging as one of the greatest threats to the health of populations worldwide. Globally, it has been estimated that the number of individuals with diabetes will rise from 171 million in 2000 to 366 million in 2030. It is associated with increased risks of micro vascular complications, including retinopathy, nephrophy and neuropathy. It also increases the risks of macro vascular diseases, including coronary heart disease, stroke and peripheral vascular disease. 

On a daily basis for three months, study patients received either one tablet of Preterax (2.0 mg perindopril / 0.625 mg indapamide) or a placebo, on top of any existing therapy such other blood pressure lowering drugs, or statins to lower cholesterol. After three months, the dose was doubled (4.0 mg / 1.25 mg). Treatment was continued until the completion of follow-up (5.5 years).

The multicentre, placebo-controlled study was conducted in 215 clinical centres selected from Australasia, Asia, Europe and North America. The trial randomised 11,140 type 2 diabetics aged 55 or over who had a high risk of vascular disease. There are two primary study outcomes – a composite of major macro vascular complications (stroke, MI, cardiovascular death), and a composite of major micro vascular complications (eye and renal disease).