Intensive glucose control reduces surrogate, but not clinical, renal outcomes in type 2 diabetes

A meta-analysis included five randomized, controlled trials (with more than 28,000 patients) comparing intensive glucose control to standard glucose control in outpatients with stable type 2 diabetes. The analysis revealed that intensive glucose control reduced microalbuminuria and macroalbuminuria more than standard treatment. However, the groups did not differ on the other measured outcomes: doubling of serum creatinine level, development of end-stage renal disease (ESRD) and death from renal disease.

The study was published by Archives of Internal Medicine on May 28. The following commentary by Eugene C. Corbett Jr., MD, MACP, was published in the ACP Journal Club section of the Nov. 20 Annals of Internal Medicine.

In their meta-analysis, Coca and colleagues focused on shorter-term (albuminuria), mid-stage (creatinine doubling), and end-stage (ESRD, death) outcomes in adults with type 2 diabetes of varying durations. They concluded that intensive therapy had short-term benefits, but evidence was insufficient to determine its effects on longer-term clinical outcomes compared with standard therapy. There was a positive association between lower hemoglobin (Hb) A1c levels and reductions in microalbuminuria and macroalbuminuria. The authors discussed major limitations of the review, which included low overall rates of mid-stage and end-stage outcomes, and heterogeneity among several study characteristics.

What useful information might clinicians take away from this study? First, patients who have close to normal glucose regulation will develop less albuminuria in the short term. Second, better long-term and longitudinal evidence is needed to link albuminuria to the rate and degree of loss of nephron function over time. The results of the review by Coca and colleagues are insufficient for this purpose, especially given the lack of long-term follow-up in some of the included studies. Third, a better understanding of the methods of intensive glucose control is needed. Sustained intensive lifestyle changes alone, including weight loss and its attendant reduction in insulin resistance, accompanied by meaningful levels of regular physical activity, reverses the pathophysiologic mechanism of type 2 diabetes. This approach probably involves less treatment risk and, perhaps, better long-term outcomes than a primarily intensive pharmacologic approach to glucose regulation.

Finally, do the results of this study mean that efforts to achieve close to normal HbA1c levels in type 2 diabetes will not prevent ESRD and its complications? Given the limitations of the evidence to date, it may be too early to abandon intensive glycemic control for type 2 diabetes.