What were the key findings of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial regarding glucose control in type 2 diabetes?

From the Guidelines

The ACCORD trial found that intensive glucose control in type 2 diabetes patients did not reduce cardiovascular events and was actually associated with increased mortality. The trial, which enrolled over 10,000 high-risk patients with type 2 diabetes, compared standard therapy targeting HbA1c of 7.0-7.9% with intensive therapy targeting HbA1c below 6.0% 1. After approximately 3.5 years, the intensive therapy arm was stopped early due to a 22% higher relative risk of death (257 vs. 203 deaths) 1. While intensive control did reduce nonfatal heart attacks slightly, this benefit was outweighed by the increased mortality risk. The intensive therapy group experienced significantly more severe hypoglycemia requiring assistance and greater weight gain than the standard therapy group 1. These findings dramatically changed diabetes management guidelines, establishing that very tight glucose control (HbA1c <6.5%) may be harmful in older patients with established cardiovascular disease or multiple risk factors 1. The study suggests that diabetes treatment should be individualized, with less aggressive glucose targets for patients with longer diabetes duration, established cardiovascular disease, or history of severe hypoglycemia 1. Some key points to consider when interpreting the results of the ACCORD trial include:

• The trial was stopped early due to increased mortality in the intensive therapy arm 1
• The intensive therapy group had more severe hypoglycemia and weight gain than the standard therapy group 1
• The findings of the ACCORD trial have been supported by other studies, such as the ADVANCE and VADT trials 1
• The results of these trials suggest that glycemic targets should not be lowered to HbA1c <6.5% in patients with a history of cardiovascular disease or the presence of vascular risk factors 1
• The American Diabetes Association has issued guidelines for glycemic targets in patients with diabetes, taking into account the results of the ACCORD and other trials 1

From the Research

Overview of the ACCORD Trial

• The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial was a randomized, multicenter, double 2 x 2 factorial design study involving 10,251 middle-aged and older participants with type 2 diabetes who were at high risk for cardiovascular disease (CVD) events 2.
• The trial aimed to test the effects of three medical treatment strategies to reduce CVD morbidity and mortality.

Key Findings

• The glycemia trial tested the hypothesis that a therapeutic strategy targeting a glycosylated hemoglobin (HbA1c) level of <6.0% would reduce the rate of CVD events more than a strategy targeting an HbA1c level of 7.0%-7.9% 2.
• However, the study was terminated early because more people had died in the intensive-treatment group than in the standard-treatment group (257 vs. 203) 3, 4.
• The results showed that intensive glucose lowering increased mortality and did not significantly reduce major cardiovascular events 4.
• A machine learning analysis of the ACCORD trial identified characteristics associated with decreased or increased mortality risk from glycemic therapy, including age, BMI, and hemoglobin glycosylation index (HGI) 5.

Subgroup Analysis

• A subgroup analysis of the ACCORD trial found that intensive glucose lowering increased the risk of cardiovascular disease and total mortality in younger participants, whereas it had a neutral effect in older participants 6.
• The analysis also found that older participants experienced higher annualized rates of severe hypoglycemia than younger participants, regardless of treatment arm 6.

Adverse Events

• The trial found that hypoglycemia requiring assistance and weight gain of more than 10 kg were more frequent in the intensive-therapy group 4.
• Severe hypoglycemia was more common in older participants than in younger participants, regardless of treatment arm 6.