The largest-ever clinical trial of diabetes treatments has found no evidence that receiving intensive treatment to lower blood glucose raises the risk of death among diabetics.
The findings of the Advance study, involving 11,140 high-risk patients with type 2 diabetes, are completely in contrast with the findings from Accord trial involving 10,251 of such patients.
The earlier Accord trial had cut short the intensive glucose control arm of the study 18 months because a data review revealed that patients who received intensive treatment to lower blood glucose are at higher risk for death. Though the trial will be continued, patients will be switched from the intensive treatment arm to the less intensive, standard treatment arm.
"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," said 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," he said.
Type 2 diabetes is responsible for an increased risk of many complications, especially cardiovascular disease—the leading cause of death in people with diabetes.
Both the studies looked at 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 type 2 diabetes patients. A successful reduction in overall and cardiovascular mortality in the intensive blood pressure arm has earlier been reported from the ADVANCE trial.
In both studies, the intensive treatment arm aimed at blood glucose levels below the ones suggested in current treatment guidelines as it has been indicated in previous studies 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, involving 20 countries worldwide including Canada, the intensive blood glucose lowering program targeted at reducing levels of hemoglobin A1c (a marker of long term blood glucose control) to more than or equal to 6.5pct. Its treatment included a sulfonylurea drug, gliclazide modified release, for all patients, and a number of other agents for patients who are unable to reach target blood glucose levels. The trial started in 2001 and patients were followed for an average of five years.
As 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 find out the chances of a similar excess risk of mortality. This committee suggested that data did not offer any verification of the unfavourable 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. 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," said Study Director, Dr. Anushka Patel, from The George Institute in Sydney, Australia.
The final data from the Advance trial may 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.