These results from ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation) were presented at the European Association for the Study of Diabetes (EASD) in Rome Wednesday. It is considered the largest study of its kind.
Previous findings from ADVANCE have shown that tight control of blood glucose with a regimen based on gliclazide (modified release) reduces major kidney complications, while routine blood pressure lowering with the fixed combination of perindopril and indapamide significantly reduces the risk of death, as well as the risks of heart and kidney disease. This new analysis of the joint effects of these two treatments has revealed even greater protection in a multi-factorial approach to treating diabetes.
Chief investigator, Professor John Chalmers from The George Institute for International Health, Australia said, "The combination of routine blood pressure lowering and tighter glucose control in ADVANCE confers very substantial benefits with reductions of one third for serious kidney disease, one quarter for cardiovascular death and close to one fifth for death from any cause. These results provide powerful incentives for the millions of people living with type 2 diabetes."
Diabetes mellitus is one of the greatest threats to the health of populations worldwide. Globally, there are over 250 million people with diabetes and that number is estimated to rise to around 400 million in 2025. ADVANCE was initiated and designed by researchers at Australia's George Institute for International Health and involved a group of independent medical researchers from 20 countries worldwide. The study involved 11,140 patients with type 2 diabetes who were treated and followed for five years.
The new analysis confirms that the effects of the two treatments are independent of one another for all pre-specified clinical outcomes, suggesting that the separate effects of intensive glucose control and routine blood pressure lowering are fully additive.
The study was designed to determine the separate and the joint effects of routine blood pressure lowering, regardless of the starting blood pressure level, and of tighter glucose control regardless of the starting blood sugar level, on the risks of complications in patients with type 2 diabetes.
"Overall, the ADVANCE study has continued to find positive benefits for people living with type 2 diabetes across the world. Both blood pressure and blood glucose control have important roles to play in diabetes management," concluded Professor Chalmers.
ADVANCE was designed, conducted, monitored, analysed and reported by a collaborative medical research group supported by the Australian Government's National Health and Medical Research Council after full peer review.
For the blood pressure lowering comparison as published in Lancet in 2007, half received daily treatment with a single tablet containing fixed combination of two blood pressure lowering drugs (perindopril and indapamide) and half received matching inactive placebo.
For this comparison, the key findings of ADVANCE were:
Reduced the risk of death from any cause by 14%
Reduced the risk of death from cardiovascular disease by 18%.
In absolute terms, one death would be avoided for every 79 patients treated with the fixed combination of perindopril and indapamide for five years.
The risk of coronary heart disease events was reduced by 14% and the risk of new or worsening kidney disease was reduced by 21%.
For the blood glucose comparison, one half of the patients received an intensive glucose lowering regimen based on the sulfonylurea, modified-release gliclazide, with other drugs as required, targeting an haemogloboin A1c level of 6.5% or below, and the other half were treated according to local guidelines.
For this comparison the key findings of ADVANCE were:
Achieving the target HbA1c level of 6.5%, with safety,
Significant reductions of 10% in the overall risk of serious diabetes complications , of (21%) in kidney disease and of 30% in the development of proteinuria, a well established marker of increased cardiovascular risk.
Achieving a positive trend towards reduction in the risk of cardiovascular death (12%), although not statistically significant.