Intensive blood glucose control can improve renal outcomes in patients with type 2 diabetes, including a significant reduction in the likelihood of progressing to end-stage renal disease (ESRD), according to a large study.

The prospective study included 11,140 patients with type 2 diabetes randomly assigned to follow either an intensive or standard glucose-lowering strategy. After a median follow-up of five years, the intensive group had a significant 65% decreased risk of ESRD compared with the standard group, investigators led by Vlado Perkovic, MBBS, PhD, of the University of Sydney in Australia, reported online in Kidney International. The mean hemoglobin A1c (HbA1c) level was 6.5% in the intensive group compared with 7.3% in the standard group.

In addition, the intensive group experienced a 30% reduction in the risk of macroalbuminuria and a 9% reduction in the risk of microalbuminuria. The progression of albuminuria was decreased significantly by 10% and its regression increased significantly by 15%.

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The number of subjects needed to treat over five years to prevent ESRD event ranged from 410 in the overall study to 41 in those with macroalbuminuria at baseline.

“These data suggest that intensive glucose lowering may be an important strategy to curb the growing number of individuals receiving dialysis as a result of diabetic nephropathy around the world,” Dr. Perkovic’s group concluded.

The target HbA1c level for patients assigned to the standard glucose-lowering group was defined by local guidelines. The target level for the intensive group was 6.5% or less. Patients assigned to the intensive group started on gliclazide MR (20-120 mg daily) and were required to discontinue any other sulfonylurea. The timing, selection, and dose of all other treatments used to achieve the target were at the discretion of the treating physician.

Mean systolic blood pressure were 1.6 mm Hg lower on average in the intensive group compared with the standard group, and adherence to BP-lowering drugs was slightly higher (75.2% vs. 72.5%), but the investigators said “it is unlikely that these small differences accounted for the observed effects.”

“The new data presented here provide the strongest evidence yet that intensive glucose-lowering regimens may protect against the development of ESRD, one of the most devastating and expensive complications of diabetes,” the researchers noted. “The results were consistent across different levels of HbA1c, kidney function, and albuminuria.”

Commenting on the new study, Barry I. Freedman, MD, Chief of the Section on Nephrology at Wake Forest School of Medicine in Winston-Salem, N.C., noted that the finding that intensive glucose lowering slows progression to ESRD is important and consistent with other studies demonstrating renoprotective effects of intensive glucose lowering.

“Anything that can reduce the number of patients with diabetes who progress to dialysis is critically important because diabetes is the number one cause of end-stage renal disease in the Western world,” said Dr. Freedman, who has been involved in numerous studies of chronic kidney disease in patients with diabetes but did not participate in the new study.

In addition, he noted that the reduction in heavy proteinuria was quite striking, but this does not necessarily translate into preservation of renal function. “Frankly, development of end-stage renal disease is due to a reduction in kidney function. Reduction in heavy proteinuria may be a different phenomenon. Protein in the urine does not always equate with loss of kidney function.”

One of the confounding issues in this study was whether the reduction in progression to dialysis or development of heavy proteinuria was strictly due to the lower blood sugars, Dr. Freedman told Renal & Urology News. In his view, the lower systolic BP achieved in the intensive group could have influenced findings, as it is well established that lowering BP slows development and progression of diabetic kidney disease.

The intensive group showed greater adherence to BP-lowering drug therapy, and this could reflect greater therapeutic adherence in general, which could have had a positive effect on outcomes, he said. Furthermore, unlike previous studies that used many different medications to lower blood sugar, the new study assigned patients in the intensive group to receive one particular sulfonylurea, Dr. Freedman noted, adding that it is possible that this drug has a unique effect that benefited the intensive group.