Aggressive Diabetes Therapy May Raise Death Risk
March 2, 2011 — New results from a large government-run trial confirm that very aggressive treatment to lower blood sugar is associated with an increased risk of death in people with type 2 at high risk for heart attack and stroke.
The five-year follow-up from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study confirms findings that ended the trial’s aggressive blood sugar control arm due to safety concerns.
The study was designed to determine if intensive blood sugar, blood pressure, or cholesterol lowering with intensive treatment would improve outcomes and reduce deaths among people with type 2 diabetes with heart disease or multiple cardiovascular risk factors.
In February 2008, the National Heart, Lung, and Blood Institute (NHLBI) announced that the intensive blood sugar lowering arm of the study would be halted 18 months early after investigators reported an increase in deaths among patients in the aggressive treatment group.
Various diabetes drugs were used to lower blood sugar in the trial. The higher death rate in the tight control arm was not blamed on any single treatment.
FDA Drug Restrictions
Last fall, the FDA announced tight restrictions on GlaxoSmithKline’s diabetes drug Avandia (rosiglitazone), citing an elevated risk of heart attacks, strokes, and deaths among users.
ACCORD investigator William T. Friedewald, MD, of Columbia University, tells WebMD that even though Avandia was a treatment option in the study, there is no evidence that it was responsible for the increase in heart-related deaths.
“As you can imagine, we looked at this very carefully, but there was nothing that suggested any increase in mortality or any other end point that was specific to this drug,” he says.
In fact, the analysis failed to identify any single diabetes drug or drug combination that explained the excess in deaths among the most aggressively treated patients.
American Diabetes Association Chief Science and Medical Officer David M. Kendall, MD, who was a study investigator, says an analysis of the data suggests patients who failed to respond to very aggressive treatment had the greatest risk of dying.
“What we don’t know is if they were at higher risk because of the intensive treatment or if there was something else that made them harder to treat,” Kendall says.
5-Year Follow-up Confirms Risk
A total of 10,251 high-risk patients were originally enrolled in the ACCORD study.
The targeted blood sugar level in the intensive glucose lowering arm was less than 6% hemoglobin A1c (HbA1c), while the target for the standard treatment arm was 7% to 7.9% HbA1c.
Over an average of three-and-a-half years of treatment, 257 deaths occurred in the intensive therapy group, compared to 203 deaths in the standard treatment group, representing three additional deaths per 1,000 people treated each year.
The newly reported findings, published March 3 in the New England Journal of Medicine, extend the follow-up to five years.
Study co-investigator Robert Byington, MD, of Wake Forest University School of Medicine, tells WebMD that the longer follow-up confirms the earlier mortality picture.
“There was the possibility that the mortality difference might go away with more follow-up, but that is not what we found,” he says.
The researchers conclude that intensive treatment to reduce blood sugar to below 6% HbA1c cannot be recommended for patients with type 2 diabetes who have a high risk for heart attack and stroke.
Kendall says the recommendation agrees with current American Diabetes Association treatment guidelines.
“Achieving (hemoglobin A1c) levels in the 7% range provides significant protection for the eyes, the nerves, and the kidneys, but going lower does not seem to add additional benefits in terms of cardiovascular risk,” he says.