Intensive glucose control in patients with type 2 diabetes can reduce the risk of progression to end-stage renal disease but the number needed to treat is large, according to a post hoc analysis of the ADVANCE trial. The analysis appears in Kidney International (2013;83:517-524).
The authors (an international team calling itself the ADVANCE Collaborative Group) write that the findings “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.”
ADVANCE enrolled 11,140 patients with type 2 diabetes (mean age: 66 years) with a mean hemoglobin (Hb) A1c value of 7.5%. It was conducted in 215 centers from 20 countries. Patients were randomized to intensive glucose control (5571—gliclazide as initial therapy with addition of other drugs as required to reach target HbA1c of ≤6.5%) or to standard control (5569—the use of any drugs except gliclazide with no specified target HbA1c).
After a median of 5 years, mean HbA1c levels were 6.5% in the intensively treated group and 7.3% in the standard group. There were 20 occurrences of ESRD in standard-treatment patients and 7 in intensively treated patients. Although this difference was significant, (P=.017), the number needed to treat (NNT) with intensive glycemic control to prevent 1 case of ESRD over 5 years was 410. The NNT declined to 85 when considering individuals with both an estimated glomerular filtration rate <60 mL/min/1.73m2 and either microalbuminuria or macroalbuminuria, and declined even further to 41 in patients who had macroalbuminuria at baseline.
There were no significant differences between groups in the rates of renal death or a composite of ESRD and renal death.
In those who were normoalbuminuric at baseline, new-onset microalbuminuria was reduced by 9% (P=.01) with intensive control relative to standard control. Among those who were normoalbuminuric or microalbuminuric at baseline, the risk of developing macroalbuminuria was reduced by 30% (P<.001) with intensive glucose control. The rate of progression of albuminuria by 1 stage or more was reduced from 25.3% to 23.3% with intensive control (P=.002), and regression to normoalbuminuria occurred more often in the intensively treated group (56.3% vs. 50.2%; P=.0002). There was no reduction in the risk of doubling of serum creatinine with intensive control.
In commentary that accompanied the paper (2013;83:346-348), the commentators (from the University of Alberta, Edmonton, Canada, and the Alberta Kidney Disease Network) write that this post hoc analysis is the only analysis to suggest that this intensive strategy may reduce the incidence of the clinically relevant outcome ESRD. They note that an HbA1c target <6.5% has been associated with excess mortality in patients with diabetes and established chronic kidney disease and no reduction in the incidence of cardiovascular events, and has exposed patients to the risks of hypoglycemia. As such, they conclude that “an A1ctarget <6.5% for type 2 diabetes should be used cautiously, if at all—perhaps only in well-informed patients who are younger, at lower risk for hypoglycemia, and free of symptomatic cardiovascular disease.”