Type 2 Diabetes and Glycated Hemoglobin (HbA1c)
Where Have We Been and Where Are We Going?
December 2010
Volume 1, Issue 1

Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial

Lancet. 2010;376(9739):419-430

Introduction:  It is well-known that hyperglycemia is associated with an increased risk of cardiovascular complications for people with type 2 diabetes.  This analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial looked at if a reduction of glycated hemoglobin (HbA1c) decreases the rate of microvascular complications in type 2 diabetics.

Methods:  Using the ACCORD trial data, the group looked at prespecified composite outcomes.  They were:  dialysis or renal transplantation, high seum creatinine (>291.7 µmol/L), or retinal photocoagulation or vitrectomy (first composite outcome); or peripheral neuropathy plus the first composite outcome (second composite outcome).  Additionally, 13 prespecified secondary measures were assessed; they were measures of kidney, eye, and peripheral nerve function.  The analysis was done for all patients who were assessed for microvascular outcomes; it did not matter what treatment they were receiving as part of the ACCORD trial or how compliant they were to the therapies.

Results:  In the ACCORD trial, the patients in the intensive blood glucose control group were transitioned to the standard blood glucose control before the end of the study; this was because of higher mortality in the intensive-therapy group.  At the time of transition, 443 out of 5,107 patients in the intensive-therapy group had the first composite outcome; it was 444 out of 5,108 in the standard-therapy group (hazard ratio, 1.00; 95% CI, 0.88-1.14; p=1.00).  The second composite outcome was recorded in 1,591 out of 5,107 patients in the intensive-therapy group; it was noted in 1,659 out of 5,108 in the standard-therapy group (hazard ratio, 0.96, 0.89-1.02; p=0.19).

At the end of the study, the results were similar.  First composite outcome was noted in 556 out of 5,119 vs. 586 out of 5,115, respectively (hazard ratio, 0.95; 95% CI, 0.85-1.07; p=0.42).  The second composite outcome was noted in 1,956 out of 5,119 vs. 2,046 out of 5,115, respectively (hazard ratio, 0.95; 0.89-1.01; p=0.12).

The risk of advanced measure of microvascular outcomes was not reduced by intensive blood glucose therapy; intensive blood glucose therapy did delay the onset of albuminuria and some measures of eye complications and neuropathy.  There were 7 secondary measures that favored intensive blood glucose therapy at the end of the ACCORD trial (p<0.05).

Conclusions:  When considering intensive blood glucose therapy, the microvascular benefits of the therapy should be considered with the increase in total and cardiovascular disease-related mortality, increased weight gain, and high risk for severe hypoglycemia.