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30-05-2012 | Article

No extra renal protection from tight glucose control


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MedWire News: Aggressive glucose-lowering treatment reduces the risk for micro- and macroalbuminuria in comparison with conventional treatment in patients with Type 2 diabetes, but does not reduce their risk for end-stage renal disease (ESRD) or death from renal disease, report authors of a systematic review.

In seven randomized trials involving 28,065 adults with Type 2 diabetes, intensive glucose control reduced the risk for both microalbuminuria (risk ratio [RR]=0.86) and macroalbuminuria (RR=0.74) compared with standard glucose control. But the aggressive therapy did not prevent doubling of serum creatinine levels (RR=1.06, 95% confidence interval [CI]: 0.92-1.22), ESRD (RR=0.69, 95% CI: 0.46-1.05), or death from renal disease (RR=0.99).

"Our analysis demonstrates that, after 163,828 patient-years of follow-up in the seven studies examined, intensive glycemic control lessens albuminuria, but data are lacking for evidence of a benefit for clinically important renal end points," write Steven Coca (Yale University, New Haven, Connecticut, USA) and co-authors in Archives of Internal Medicine.

They note that their finding of a nonsignificant trend towards reduction of ESRD was "a surprising observation given the very tight precision and null findings for the end point of doubling of the serum creatinine level that must precede ESRD."

The investigators searched three databases spanning 6 decades for randomized trials comparing surrogate endpoints (albuminuria) with clinical endpoints. They identified seven such studies, and pooled the data to determine outcomes.

They conducted a meta-regression analysis that controlled for median date of enrollment, years since Type 2 diabetes diagnosis, duration of therapy, difference in achieved glycated hemoglobin A1c (HbA1c), and median achieved HbA1c. The authors found that studies in which intensive therapy produced larger magnitude reductions in HbA1c were associated with greater reductions in both surrogate endpoints.

In an invited commentary, David Nathan (Massachusetts General Hospital, Boston, USA) says that longer follow-up is needed to determine the benefit of intensive glucose control on clinical outcomes such as renal and cardiovascular disease.

He writes: "Given this background, the studies included in the meta-analysis by Coca et al, with the possible exception of the UKPDS [United Kingdom Prospective Diabetes Study] long-term follow-up, were far too brief to address the effects of intensive therapy on end-stage renal disease. Their short duration and low absolute rates of severe renal outcomes, acknowledged by the authors, precluded such an analysis.

"If the authors were interested in whether intensive therapy had a short-term toxic effect on the development of kidney disease, which has not been suggested, their meta-analysis might have made more sense."

By Neil Osterweil