Role of Intensive Glucose Control in Development of Renal End Points in Type 2 Diabetes Mellitus: Systematic Review and Meta-Analysis

Study Questions:

What are the benefits of intensive versus conventional glucose control on kidney-related outcomes for adults with type 2 diabetes?

Methods:

Three databases were systematically searched (January 1, 1950, to December 31, 2010) with no language restrictions to identify randomized trials that compared surrogate renal endpoints (microalbuminuria and macroalbuminuria) and clinical renal endpoints (doubling of the serum creatinine level, end-stage renal disease [ESRD], and death from renal disease) in patients with type 2 diabetes receiving intensive glucose control versus those receiving conventional glucose control. The authors examined the relationship between intensive glucose control and risk for all study outcomes using risk ratio (RR) and risk difference measures.

Results:

The investigators evaluated seven trials involving 28,065 adults who were monitored for 2-15 years. Compared with conventional control, intensive glucose control reduced the risk for microalbuminuria (RR, 0.86; 95% confidence interval [CI], 0.76-0.96) and macroalbuminuria (RR, 0.74; 95% CI, 0.65-0.85), but not doubling of the serum creatinine level (RR, 1.06; 95% CI, 0.92-1.22), ESRD (RR, 0.69; 95% CI, 0.46-1.05), or death from renal disease (RR, 0.99; 95% CI, 0.55-1.79). Meta-regression revealed that larger differences in glycated hemoglobin HbA1c between intensive and conventional therapy at the study level were associated with greater benefit for both microalbuminuria and macroalbuminuria. The pooled cumulative incidence of doubling of the serum creatinine level, ESRD, and death from renal disease was low (<4%, <1.5%, and <0.5%, respectively) compared with the surrogate renal endpoints of microalbuminuria (23%) and macroalbuminuria (5%).

Conclusions:

The authors concluded that evidence is lacking that intensive glycemic control reduces the risk for significant clinical renal outcomes.

Perspective:

This systemic review and meta-analysis suggests that intensive glycemic control lessens albuminuria, but data are lacking for evidence of a benefit for clinically important renal endpoints such as doubling of the serum creatinine level, ESRD, or death from renal disease. Given the low incidence of clinical renal outcomes, coupled with the apparent lack of convincing benefit of intensive glycemic control to prevent chronic kidney disease and ESRD in patients with newly diagnosed or existing type 2 diabetes mellitus, there is little rationale to initiate intensive glycemic control in midstage of the disease with the aim of preventing renal failure. The effectiveness of intensive therapy when initiated early in the course of diabetes in preventing renal failure requires further study.

Keywords: Coca, Hemoglobin A, Glycosylated, Kidney Diseases, Kidney Failure, Chronic, Blood Glucose, Cardiology, Diabetes Mellitus, Type 2, Cardiovascular Diseases, Hypoglycemic Agents, Confidence Intervals, Renal Insufficiency, Chronic


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