May 29th, 2012
More Evidence Against Tight Glycemic Control
Along with tight blood pressure control and RAAS blockade, most nephrologists recommend tight glycemic control (i.e., HbA1C < 7) for patients with type 2 diabetes, with the goals of reducing incident CKD or CKD progression. Data from observational studies has shown that tight glycemic control is associated with less albuminuria. Thus, conventional wisdom has been that tight glycemic control will improve albuminuria, and a reduction in albuminuria, in turn, should lead to less CKD. However, definitive data on the true efficacy of this strategy was lacking.
With the recent completion of the ACCORD, ADVANCE, and VADT trials, a larger body of evidence involving 28,065 patients and 163,828 patient-years of follow-up indicates that we still don’t have evidence that targeting lower HbA1C goals reduces the incidence of CKD, ESRD, or renal-related death, as published in our systematic review and meta-analysis in Archives of Internal Medicine. While the cumulative incidence of ESRD (1.5%) and renal-related death (<1%) were very low, thus underpowered to detect a difference, the outcome of doubling of serum creatinine (occurred in 4%), provided a tight confidence interval that bracketed a relative risk of 1.06 (95% CI 0.92-1.22), truly suggesting no benefit of tight glycemic control for this endpoint, even had the pooled sample size been larger. Given the fact that recent trials examining intensive glycemic control have shown no benefit for cardiovascular disease or all-cause mortality, trying to achieve tight glycemic control for the purpose of prevention of chronic kidney disease may not be worth it due to costs, patient effort, hypoglycemic risks, etc. Furthermore, even if there is a true biologic benefit for prevention of CKD, the low absolute rates of CKD events makes the achievable absolute risk reduction via intervention very small, resulting in a very high number needed to treat to prevent one CKD event. Therefore, it will take a very large randomized controlled trial with long duration of follow-up to prove that intensive glycemic control is beneficial for CKD. Until then, “less may be more”.