This article is more than 5 years old. Information may no longer be current.
ACCORD: Intensive glucose control not to blame for excess mortality
Click Here to Manage Email Alerts
American Diabetes Association 69th Scientific Sessions
Low blood glucose levels do not explain the excess mortality in patients with type 2 diabetes in the ACCORD trial, according to a new analysis.
The researchers confirmed the estimate that was reported last year of a 22% increased risk for death associated with ACCORD’s intensive treatment strategy, but new analyses did not confirm the proposed theory that low HbA1c levels might be the cause.
“Our findings do not support the view that rapid reduction of glucose levels or lower average HbA1c led to the excess risk for death with the intensive glycemic strategy,” said Matthew C. Riddle, MD, professor of medicine at Oregon Health Science University. Riddle presented the new analysis at the American Diabetes Association’s 69th Scientific Sessions on Tuesday.
ACCORD researchers enrolled 10,251 patients with type 2 diabetes and randomly assigned them to intensive glucose control (HbA1c <7%) or standard control (7-7.9%). The Data Safety Monitoring Board terminated ACCORD in February 2008 after 3.4 years due to increased deaths in the intensive treatment arm (257 vs. 203; P=.04).
“There is no smoking gun” with lower HbA1c, Riddle said at a press conference.
In fact, lower HbA1c levels had a positive effect on mortality in patients assigned to both intensive and standard glucose control. Each 1% lower HbA1c level was associated with a statistically significant 56% lower relative risk for mortality in the intensive therapy group (HR=1.66; P=.0001) and a 14% lower risk in the standard therapy group (HR=1.14; P=.07). The highest risk for death remained after statistical adjustment for age, duration of diabetes or prior CV events.
This finding suggests that lower blood glucose levels “may be a worthy target in some patients,” Riddle said.
In addition, patients who rapidly lowered their HbA1c levels during the first year of treatment appeared to have a lower risk for death. Mortality risk increased for the standard therapy group with HbA1c levels of 6-9% but increased in the intensive therapy group only for those with HbA1c >7%. Excess mortality in the intensive control group occurred among those who were unsuccessful in reaching a target goal at or near 6%.
“The paradox of these two juxtaposed, seemingly contrary findings was found to relate to the markedly different relationship between risk of death and average HbA1c between the groups. The excess risk of death with intensive glucose control occurred in those participants whose HbA1c was >7%, not below,” Riddle said during the symposium.
Unexpected relationship with HbA1c, hypoglycemia
An analysis of hypoglycemia — defined as blood glucose <50 mg/dL or symptoms consistent with hypoglycemia recovered with glucagon or an oral carbohydrate — was also presented during the symposium.
The researchers reported 451 deaths in both ACCORD treatment groups, and 7% of individuals had at least one severe hypoglycemic event requiring medical assistance.
“HbA1c was associated with hypoglycemia but not in the relationship we expected,” said Denise Bonds, MD, MPH, project officer for ACCORD at the National Heart, Lung and Blood Institute, National Institutes of Health.
Severe hypoglycemia was associated with higher risk for death in both treatment groups but a lower risk in the intensive group vs. standard group (HR=1.28 vs. HR=2.87). Further, risk for hypoglycemia was lower in the intensive control group who achieved the target goal faster compared with the standard group (HR=0.86 vs. HR=0.72). Importantly, hypoglycemia did not account for overall mortality findings.
“Hypoglycemia was felt to play no role in most deaths,” Bonds said. Few deaths occurred within 90 days of a documented episode of severe hypoglycemia.
Analyses to identify the cause of the increase in mortality, such as weight gain or a particular drug or combination of drugs, are underway. Other ACCORD studies for BP and lipid control will end on June 30, 2009, and a complete analysis of all three studies is expected in the next year.
In the meantime, “the analyses suggest that, using an intensive strategy, some persons with type 2 diabetes can safely achieve HbA1c levels <7%,” and others who do not have the same reductions may be at risk if they persist with this strategy, Riddle concluded. – by Katie Kalvaitis
For more information:
- New analyses from ACCORD and VADT. Presented at: American Diabetes Association’s 69th Scientific Sessions; June 5-9, 2009; New Orleans.