The surprising and much-publicized early findings from the ACCORD study, which showed a slightly increased risk of death among certain people with Type 2 diabetes who used intensive drug therapy to lower blood glucose levels, have prompted researchers conducting a similar ongoing study to release early results. The ADVANCE study, which is the largest study ever of aggressive blood glucose control in people with Type 2 diabetes, has found no increase in risk of death associated with intensive treatment.
The ADVANCE trial’s 11,140 participants were followed over an average period of five years. The blood-glucose-lowering arm of the study ended in January, and confirmation of the data was more than 99% complete in mid-February according to the study’s director.
In several important ways, the studies are alike. For example, the populations in both studies were similar, with about one-third of the participants in each having a history of cardiovascular disease before the studies began. Both studies randomly divided participants into intensive-control and standard-control groups with regard to HbA1c levels (blood glucose levels over time). And in both studies, the intensive-control groups achieved the same average HbA1c level: 6.4% (although in the ACCORD trial the group was aiming for less than 6% and in the ADVANCE trial the group aimed for 6.5%). But, unlike the ACCORD researchers, the ADVANCE group—which says it is working with twice as much data as the ACCORD trial provided—has so far found “no indication of harm” associated with achieving this HbA1c level.
Until more analysis is done, the researchers will not be able to explain why the studies may have come up with different results. In addition, some differences between the two studies will need to be considered. For example, it is likely that different combinations of drugs were used to achieve intensive blood glucose control in the studies; once full analysis of the data from ADVANCE is complete, researchers will know more about these potential differences in treatment. There were also differences in the average age of participants (66 years old for ADVANCE; 62 years old for ACCORD), years of living with diabetes before the trials began (8 years for ADVANCE; 10 years for ACCORD), blood pressure levels at the beginning of the studies (higher in ADVANCE than in ACCORD), and HbA1c levels at the beginning of the studies (lower in ADVANCE than in ACCORD). The ADVANCE researchers will need to analyze all of these factors before they can draw conclusions about the risks and benefits of intensive blood glucose control in high-cardiovascular-risk groups of people with Type 2 diabetes. The ACCORD and ADVANCE investigators also have some joint analyses of data planned.
The ADVANCE trial, which took place at The George Institute for International Health at the University of Sydney in Australia, was funded in part by the pharmaceutical company Servier, which manufactures one of the drugs (the sulfonylurea gliclazide [brand name Diamicron], which is not marketed in the United States) that was used by all members of the intensive-control group in the trial.
A variety of pharmaceutical companies contributed drugs, equipment, or supplies to the ACCORD trial.
In a statement, the American Diabetes Association said that it plans to “critically examine the final data from these studies once they are publicly available later this year and will issue further recommendations at that time.” In the meantime, however, it continues to promote a general goal of an HbA1c level under 7% for people with diabetes, with higher or lower individualized goals possible based on people’s individual situations.
You can read more of DiabetesSelfManagement.com’s coverage of the ACCORD trial results in the blog entries “The ACCORD Trial Findings: What You Should Know,” “ACCORD Travesty,” and “What We’re Reading: Reactions to ACCORD.”