Intensive lowering of blood glucose can delay some of the microvascular complications common in people with type 2 diabetes (i.e., neuropathy, nephropathy, and retinopathy), but these benefits must be weighed against increases in total and cardiovascular-related mortality, increased weight gain, and severe hypoglycemia.

The intensive-glycemia-control arm (aiming for hemoglobin A1c [HbA1c] values <6%) of the ACCORD trial was halted in February 2008, after a median of 3.7 years of patient participation, due to an increased rate of all-cause mortality. Patients were moved to the standard-therapy arm (in which HbA1c targets of 7.0% to 7.9% with a mean of 7.5% were targeted) for the planned remainder of the median 5.0 years of follow-up to June 2009.

Faramarz Ismail-Beigi, MD, and other ACCORD investigators recently reported the results of the secondary microvascular outcomes in the 5,107 participants transitioned from intensive to standard therapy and the 5,108 from the original standard arm (Lancet. 2010 Jun 29, published online ahead of print). Intensive therapy did not reduce the incidence of cardiovascular disease, and the two groups did not differ in overall measures of microvascular health (e.g., progression rates to kidney failure, major vision loss, or advanced peripheral neuropathy). 

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However, compared with standard treatment, intensive glucose-lowering did delay the onset of albuminuria, a marker of kidney disease, and some measures of eye complications and neuropathy: The intensive group had fewer cataract extractions as well as sharper vision and better nerve function scores than the other group.

Keeping in mind that intensive glycemia therapy in ACCORD increased all-cause mortality and led to increased BMI and a threefold increase in frequency of severe hypoglycemia, the authors advised caution in the pursuit of intensive glycemic control for prevention of microvascular complications. “An HbA1c target of 6.0% or less with present strategies seems imprudent,” they added.