Low A1C Not to Blame for ACCORD Death Rate; Questions Remain

The Action to Control Cardiovascular Disease in Diabetes (ACCORD) study made headlines in 2008 when its intensive blood-glucose-lowering arm was stopped early due to an unexpectedly high death rate. At the time, some in the medical field theorized that episodes of hypoglycemia (low blood glucose), rapidly lowering blood glucose levels, or maintaining low A1C levels were to blame. However, recent analysis shows that it was not these factors, but rather unsuccessful attempts to lower A1C, that were associated with the increased death rate.

The ACCORD study sought to determine whether intensive lowering of blood glucose, blood pressure, or blood lipids (fats) could decrease the rate of heart attack, stroke, or cardiovascular death in people with Type 2 diabetes compared to conventional treatment approaches. Over 10,000 people were enrolled in the glucose-lowering arm of the trial and were randomly assigned to either a standard or an intensive blood-glucose-lowering strategy. People in both groups received glucose-lowering medicines based on their needs and A1C goals; those in the intensive management group had a lower A1C target and were more likely to be on a combination of drugs. When the study was stopped, the intensive group had an average A1C of 6.4% and the standard group had an A1C of 7.5%.

According to the authors of the new ACCORD analysis, the higher-than-expected death rate occurred in people in the intensive control arm who were not able to lower their A1C level below 7.0%. Looking at data gathered in the 3.4 years before the study arm was stopped, the researchers determined that the risk of death in the intensive control group increased in a linear fashion along with A1C levels from 6.0% to 9.0% and that mortality risk was only greater in the intensive group compared to the standard group when the average A1C level was greater than 7.0%.

In an interview with Endocrine Today, Matthew C. Riddle, MD, lead author of the new paper, stated that “Targeting 7% A1C or lower continues to be an evidence-based goal of treatment in Type 2 diabetes in general, but ACCORD suggested that a subgroup of patients should seek less ambitious A1C goals. Our findings support the view that we will have to consider different A1C targets and perhaps different treatment strategies for different groups of patients.”

Although the new findings appear to shed some light on the study results, questions still remain about what exactly was behind the death risk. Riddle noted that “We still don’t know why more patients in the intensive group died.”

To learn more, read the article “Culprit Identified in ACCORD Study” or see the paper’s abstract in Diabetes Care.