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

Effects of Intensive Glucose Lowering in Type 2 Diabetes

N Engl J Med. 2008;358(24):2545-2559

Introduction:  The Action to Control Cardiovascular Risk in Diabetes (ACCORD) Study Group noted that epidemiologic studies have demonstrated a relationship between glycated hemoglobin (HbA1c) levels and cardiovascular events in type 2 diabetics.  In the ACCORD trial, the group investigated if intensive blood glucose therapy—targeting normal HbA1c levels—would reduce cardiovascular events.  This was examined in patients with type 2 diabetes who had either established cardiovascular disease or additional cardiovascular risk factors.

Methods:  10,251 patients (mean age, 62.2 years; median HbA1c, 8.1%) were randomly assigned to either an intensive blood glucose control group or a standard blood glucose control group.  In the intensive-therapy group, the goal HbA1c level was below 6.0%, and in the standard-therapy group, the goal was from 7.0% to 7.9%.  38% of the patients were women; 35% of the patients had had a previous cardiovascular event.

The primary outcome assessed was a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes.

Because there was higher mortality in the intensive blood glucose control group, the intensive therapy was discontinued after a mean follow-up of 3.5 years.

Results:  At 1-year follow-up, the intensive-therapy group had a stable median HbA1c level of 6.4%; in the standard-therapy group, it was 7.5%.  The primary outcome occurred in 352 patients in the intensive blood glucose control group; it occurred in 371 patients in the standard blood glucose control group (hazard ratio, 0.90; 95% CI, 0.78-1.04; p=0.16).

257 patients died in the intensive-therapy group; 203 patients in the standard-therapy group died (hazard ratio, 1.22; 95% CI, 1.01-1.46; p=0.04).

Compared to the standard-therapy group, hypoglycemia requiring assistance and weight gain of more than 10 kg occurred more frequently in the intensive-therapy group (p<0.001).

Conclusions:  When compared to standard blood glucose control, intensive blood glucose control to achieve normal HbA1c levels for 3.5 years increased mortality and did not significantly reduce major cardiovascular events.  The ACCORD trial demonstrates a harm of intensive blood glucose control in high-risk patients with type 2 diabetes.

Next Article:
A Summary of Dr. William T. Cefalu’s Editorial “Glycemic Targets and Cardiovascular Disease”