Abstract
The ADVANCE trial: update and NEW results
JF Gautier, Paris (France)
ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation) is the largest trial undertaken today in patients with type 2 diabetes. It is a 2x2 factorial trial evaluating the effects of blood pressure lowering and blood glucose control on vascular complications, conducted in 11 140 randomized patients with type 2 diabetes, from 20 countries on 4 continents.
The first results of the Glucose Control Arm, published in 2008, reported the effects of intensive glycemic control using a Diamicron MR–based regimen and aimed at targeting an HbA1c≤ 6.5% versus conventional therapy, at a median follow-up of 5 years. This approach allowed efficient and progressive lowering of HbA1c to the target value of 6.5%.
Analysis of the first end point showed a 10% reduction (P=0.01) in the combined risk of micro- and macrovascular events. The safety of this therapeutic approach is confirmed by a positive trend in the reduction of all-cause mortality (-7%) and cardiovascular mortality (-12%).
The reduction of microvascular complications (-14%, P=0.014) was mainly due to the reduction of renal events (-21%, P=0.006) with a significant decrease in the number of subjects developing macroalbuminuria (-30%, P0.001). There was also a significant reduction in new onset microalbuminuria (-8%, P=0.03).
These results were achieved with no weight gain and with a low incidence of severe hypoglycemic events, as compared to other trials such as ACCORD, VADT and UKPDS.
New results published in 2010 confirm that tight glycemic control is efficient whatever the severity of the disease (mean HbA1c at entry, duration of diabetes), and also whatever the age and BMI of patients.
Most recently, a new analysis from ADVANCE indicates that, in patients with albuminuria at baseline, regression by at least one stage occurred in 62% of intensively treated patients, with 57% achieving normoalbuminuria. Furthermore, only 40% of subjects in the intensive control group required insulin by the end of follow-up. The average time to the introduction of insulin in the intensive group was 44 months, later than the 36 months taken to achieve the mean HbA1c of 6.5%.
These new findings confirm the safety and efficacy of the Diamicron MR–based intensive glucose control strategy used in ADVANCE, across a wide range of participants.