Montreal, February 28, 2008 - Data from the ADVANCE Study, involving 11,140 high-risk patients with type 2 diabetes, provides no evidence of an increased risk of death among those patients receiving aggressive treatment to lower blood glucose.
This contrasts findings from the 10,251 patient ACCORD trial which halted the intensive glucose control arm of the study 18 months early because a data review revealed that patients who received intensive treatment to lower blood glucose are at higher risk for death. While the trial will continue, patients will be transitioned from the intensive treatment arm (targeting A1c levels of <6.0 %) to the less intensive, standard treatment arm (targeting A1c levels of 7.0 to 7.9%).
“Unlike what we saw in ACCORD, a rigorous review of ADVANCE data by the Data and Safety Monitoring Committee shows that the treatment strategy of intensively lowering blood sugar does not pose greater risk to our patients with type 2 diabetes”, says Canadian lead investigator and member of ADVANCE Management Committee Dr. Pavel Hamet, professor of Medicine, Canada Research Chair of Predictive Genomics at Université de Montréal and Chief, Gene Medicine Services at Centre Hospitalier de l’Université de Montréal. “ADVANCE is a landmark study and will continue as planned to completion. The results will provide crucial information to help us better reduce the significant health risks associated with type 2 diabetes.”
Type 2 diabetes increases the risk of many complications, especially cardiovascular disease, which is the leading cause of death in people with diabetes. Both the ADVANCE and ACCORD studies examined the effects of intensive blood glucose and blood pressure control on the risk of cardiovascular events such as heart attack, stroke, or death from cardiovascular disease in patients with type 2 diabetes. A successful reduction in overall and cardiovascular mortality in the intensive blood pressure arm has been reported from the ADVANCE trial and published in The Lancet in September 2007.
In ADVANCE and ACCORD, the intensive treatment arm targeted blood glucose levels below those recommended in current treatment guidelines because previous studies suggest that reducing blood sugar to levels to those found in non-diabetic adults may reduce the rate of cardiovascular disease in patients with diabetes.
In the ADVANCE trial, which involves 20 countries worldwide including Canada, the intensive blood glucose lowering program aimed to reduce levels of hemoglobin A1c (a marker of long term blood glucose control) to ≤6.5%. Treatment included a sulfonylurea drug, gliclazide modified release, for all patients, and a number of other agents for those patients unable to reach target blood glucose levels. The ADVANCE trial was started in 2001 and patients were followed for an average of five years.
Because the A1c targets in ACCORD and ADVANCE are similar, and the intensive blood glucose control arm of ACCORD was stopped early, the ADVANCE mortality data was reviewed by the Data and Safety Monitoring Committee to determine if there was a similar excess risk of mortality. This committee advised that data did not provide any confirmation of the adverse mortality trend reported from ACCORD.
“Final patient visits have been completed and the ADVANCE study data base is close to finalization. We expect to have definitive results soon,” said Study Director, Dr. Anushka Patel, from The George Institute in Sydney, Australia. “At this stage, the Data Monitoring and Safety Committee have reviewed results that are more than 99% complete, so we are confident that the interim findings are a reliable guide to the final results.”
Final data from the ADVANCE trial is expected to be promising in terms of risk minimization but multiple analyses are required before conclusions can be drawn regarding the effects of intensive glucose control on patient outcomes. Additional data will be available specifically from ADVANCE, and Dr. Hamet’s team, in collaboration with Prognomix in Montréal, is performing genomic studies of the risk of complications of diabetes in this unique worldwide patient cohort.
The ADVANCE trial was conducted by an independent collaborative group of medical researchers with support from the National Health & Medical Research Council of Australia and the Institut de Recherche Internationales Servier. The results of the blood pressure control arm of ADVANCE were presented at the annual meeting of the European Society of Cardiology in Vienna, Austria in September 2007. Final results of the glucose control arm of the ADVANCE trial will be released earlier than expected, by the middle of 2008.
For further information, please contact:
Muriel Haraoui (English media relations)
HKDP Communications and Public Affairs
(514) 395-0375 X 235
mharaoui@hkdp.qc.ca
Genevieve Déry (French media relations)
HKDP Communications and Public Affairs
(514) 395-0375 X 232
gdery@hkdp.qc.ca
Sophie Langlois
Université de Montréal
(514) 343-7704
sophie.langlois@umontreal.ca
Nathalie Forgue
Centre hospitalier de l’Université de Montréal
(514) 890-8000 X 14342
The Université de Montréal with its two affiliate schools, HEC Montréal and l’École Polytechnique, constitutes the leading centre for higher learning and research in Québec, the second in Canada, and one of the largest in North America. Its faculty of medicine is the largest in Canada in terms of student enrolment, and one of the major centres for health research in the country.
The Centre hospitalier de l'Université de Montréal (CHUM) provides specialized and ultra-specialized services to its regional and supraregional clienteles. Within its more immediate coverage area, CHUM also offers general and specialized hospital care and services. The CHUM has a five-part mandate, comprising research, teaching, the assessment of technologies and healthcare intervention methods, and the promotion of an integrated-networks approach to health care. Hôtel-Dieu, Hôpital Notre-Dame, and Hôpital Saint-Luc form the CHUM, with 10,000 employees, 900 physicians, 270 researchers, 5,000 students and trainees and 800 volunteers providing services to more than 500,000 patients each year.
The George Institute for International Health is an internationally-recognized health research organization, undertaking high impact research across a broad health landscape. It is a leader in the clinical trials, health policy and capacity-building areas.
Prognomix is a Montreal biotech company focused on the discovery of genetic signatures associated with the complications of Type II Diabetes. The company is concentrating on developing a molecular diagnostic test pertinent for detection of risks to develop renal, ocular, cardiac, cerebral, vascular and other complications of diabetic disease.
The National Health & Medical Research Council of Australia is Australia's peak body for supporting health and medical research; for developing health advice for the Australian community, health professionals and governments; and for providing advice on ethical behaviour in health care and in the conduct of health and medical research.
The Institut de Recherche Internationales Servier is the international research funding arm of the French pharmaceutical company, Servier. Servier manufactures modified release gliclazide (Diamicron MR™) and the fixed combination of perindopril and indapamide (registered under the following trade names; Preterax, BiPreterax, Preterax Forte, Biprel, Noliprel, Noliprel Forte, Prelectal, Prelectal forte, Predonium, Noliprel, Coversyl Plus, Coversyl Comp, Coversum Combi, Armix Comb, Prestarium Combi, Prestarium Plus).
Reference:
ADVANCE Collaborative Group; Patel A, MacMahon S, Chalmers J, Neal B, Woodward M, Billot L, Harrap S, Poulter N, Marre M, Cooper M, Glasziou P, Grobbee D, Hamet P, Heller S, Liu L, Mancia G, Mogensen C, Pan C, Rodgers A, Williams B. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet. 2007;370:829-40.