Role of intensive glucose control in development of renal end points in type 2 diabetes mellitus: systematic review and meta-analysis intensive glucose control in type 2 diabetes

Arch Intern Med. 2012 May 28;172(10):761-9. doi: 10.1001/archinternmed.2011.2230.


Background: Aggressive glycemic control has been hypothesized to prevent renal disease in patients with type 2 diabetes mellitus. A systematic review was conducted to summarize the benefits of intensive vs 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 end points (microalbuminuria and macroalbuminuria) and clinical renal end points (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 vs those receiving conventional glucose control.

Results: We evaluated 7 trials involving 28 065 adults who were monitored for 2 to 15 years. Compared with conventional control, intensive glucose control reduced the risk for microalbuminuria (risk ratio, 0.86 [95% CI, 0.76-0.96]) and macroalbuminuria (0.74 [0.65-0.85]), but not doubling of the serum creatinine level (1.06 [0.92-1.22]), ESRD (0.69 [0.46-1.05]), or death from renal disease (0.99 [0.55-1.79]). Meta-regression revealed that larger differences in hemoglobin A1c 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 end points of microalbuminuria (23%) and macroalbuminuria (5%).

Conclusions: Intensive glucose control reduces the risk for microalbuminuria and macroalbuminuria, but evidence is lacking that intensive glycemic control reduces the risk for significant clinical renal outcomes, such as doubling of the serum creatinine level, ESRD, or death from renal disease during the years of follow-up of the trials.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Aged
  • Blood Glucose / analysis*
  • Blood Glucose / drug effects
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetic Nephropathies / etiology
  • Diabetic Nephropathies / prevention & control*
  • Disease Progression
  • Female
  • Glycated Hemoglobin A / analysis
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Kidney Failure, Chronic / etiology
  • Kidney Failure, Chronic / prevention & control*
  • Kidney Function Tests
  • Male
  • Middle Aged
  • Monitoring, Physiologic / methods
  • Prognosis
  • Randomized Controlled Trials as Topic
  • Renal Dialysis / methods
  • Risk Assessment
  • Severity of Illness Index


  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents