STOCKHOLM – An intensive glucose control regimen aiming for a hemoglobin A1c level of 6.5% or lower significantly reduced the incidence of renal events among patients with established type 2 diabetes, according to findings from a large Australian study.
The total number of renal events in 5,571 patients randomized to intensive treatment was reduced by 11% (26.9% vs. 30%), compared with 5,569 patients who followed a standard glucose control regimen, Dr. Sophia Zoungas said at the annual meeting of the European Association for the Study of Diabetes.
The data come from the glucose-lowering arm of the multination ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation) study, which examined the effects of both blood pressure lowering with perindopril/indapamide and glucose-lowering gliclazide MR in a total of 11,140 patients. Primary trial findings were reported in 2007 and 2008.
The current analysis evaluated the incidence of renal events at a median follow-up of 5 years, when the mean HbA1c level achieved was 6.5% in the intensive treatment arm and 7.3% in the standard control group, reported Dr. Zoungas, who is head of the diabetes research program at the George Institute for Global Health, Sydney.
The incidence of new microalbuminuria, defined as a urine albumin-to-creatinine ratio (UACR) of 30-300 g/mg, was reduced by 9% with intensive therapy, occurring in 23.7% of patients in that group compared with 25.7% of the standard treatment group. New-onset macroalbuminuria (UACR greater than 300 g/mg) was reduced by 30% (2.9% vs. 4.1%). New or worsening nephropathy, defined as progression of albuminuria by at least one stage (from normoalbuminuria to either micro- or macroalbuminuria) was 21% lower with intensive therapy (4.1% vs. 5.2%), and end-stage renal disease was reduced by 36% (0.4% vs. 0.6%).
All of the differences were statistically significant except for those involving end-stage renal disease, which nonetheless showed a “small but important trend,” said Dr. Zoungas, also of Monash University, Clayton, Australia.
Among 3,261 patients who had albuminuria at baseline, regression by at least one stage occurred in 61.8% of the intensive treatment group, compared with 55.8% of the standard group, for a hazard ratio of 1.15. Regression to normoalbuminuria occurred in 56.8% vs. 49.7%, with a hazard ratio of 1.2. Both were highly statistically significant, she said.
Renal benefit was seen even among those patients who had HbA1c levels less than 7% at baseline. “We could not identify an HbA1c threshold below which renal benefit was lost,” Dr. Zoungas said.
The ADVANCE study was initiated and designed by investigators at the George Institute for Global Health, and received funding from the National Health and Medical Research Council of Australia and from Servier, the maker of Preterax and Diamicron MR. Dr. Zoungas disclosed that she has received honoraria from Servier.