Intensive blood sugar control among diabetics does not increase mortality in the ADVANCE trial

February 14, 2008 By Vijayalakshmi Kunadian MBBS MD MRCP [mailto:vkunadian@perfuse.org]

Australia: A press release from the George Institute for International Health suggests that there was no increase in mortality in the intensive blood sugar control group in the ADVANCE trial, a major multinational study consisting of type 2 diabetic patients.

Recently the National Heart, Lung and Blood Institute (NHLBI) terminated the intensive blood sugar control arm due to an increase in the number of deaths in this arm of the ACCORD trial (see press release in the link below-1). This prompted the Data Monitoring and Safety Committee of the ADVANCE (Action in Diabetes and Vascular disease: PreterAx and DiamicroN MR Controlled Evaluation) trial to perform an early interim analysis to see if this trial demonstrated a similar trend. The preliminary interim results were issued in a press release from the Public Relations department of the George Institute for International Health (see link below-2). The ADVANCE trial is funded by the National Health and Medical Research Council of Australia and the Institute de Recherche Internationales Servier, Paris.

The ADVANCE trial is large study consisting of 11,140 high risk type 2 diabetes mellitus patients with a follow up for 4.5 years. This study enrolled patients from 215 centres in 20 countries to clarify two issues among patients with type 2 diabetes mellitus: (1) to determine if intensive blood pressure control reduced micro and macrovascular events and (2) to determine if an intensive blood sugar control strategy reduced micro and macrovascular events and improved outcome. The primary endpoints of this study consisted of death from cardiovascular causes, non-fatal stroke, non-fatal myocardial infarction and new or worsening diabetic eye and renal problems. The ADVANCE study commenced in July 2001 and the study to assess the effect of intensive blood sugar control therapy completed early this year.

The results of the intensive blood pressure control study using perindopril and indapamide in addition to the concurrent antihypertensive therapy were published last year in the Lancet. This demonstrated that an intensive blood pressure control resulted in a 9% (p=0.04) relative risk reduction in microvascular and macrovascular adverse events, 18% (p=0.03) reduction in cardiovascular deaths and 14% (p=0.03) reduction in death from any cause using perindopril and indapamide compared to the placebo treatment. This study also demonstrated that for every 79 patients treated one life was saved.

While exact figures are not yet available, the press release (see link below-2) on the intensive blood sugar control study indicates that there was “no evidence of increased risk of death in the intensive blood sugar control group”. This study aimed for a blood sugar HbA1C level <6.5% in contrast to <6.0% used in the ACCORD trial. The investigators note that the data collection and review on this trial is 99% complete. The complete final results of both ACCORD and ADVANCE trials are awaited.

In a statement issued in this press release (see link below-2), ADVANCE Management Committee Chairman, Professor John Chalmers, said “Doctors and patients should feel reassured that the mortality trend reported by the ACCORD study has not been found in the interim results from ADVANCE. However, we need to await more definitive analysis and reports from both studies before drawing final conclusions”.

Source

 * 1) http://public.nhlbi.nih.gov/newsroom/home/GetPressRelease.aspx?id=2551
 * 2) http://www.advance-trial.com/static/html/virtual/contents.asp?P=39