Follow-up analysis of the ACCORD controlled trial of intensive glucose lowering in patients with type 2 diabetes found that while the risk of non-fatal myocardial infarction (MI) was reduced by intensive therapy, overall mortality increased.

Type 2 diabetes is associated with increased risk of cardiovascular disease (CVD), and epidemiological studies suggested a direct relationship between hyperglycaemia and CVD adverse outcomes. As a result, controlled trials were started to investigate whether intensive blood glucose control to tight targets would improve outcomes in type 2 diabetes. The ACCORD trial randomised patients with type 2 diabetes at high CVD risk (pre-existing CVD or additional risk factors) to either intensive or conventional blood glucose control, with haemoglobin A1c (HbA1c) targets of <6.0% or 7.0 to 7.9%, respectively. The intended trial duration was 5 years, however it was stopped early after a mean of 3.5 years by the data safety monitoring committee due to an increased risk of death in the intensive group. This paper reports outcomes for intensive control between 3.5 years and 3.7 years when the trial was actually stopped, and the outcomes at five years for the two study groups.

ACCORD was large, with 10,108 participants at baseline. Before the trial was terminated, those in the intensive control group had no significant difference (P=0.13) in the primary composite outcome (nonfatal MI, nonfatal stroke, or death from cardiovascular causes) but had more deaths from any cause (primarily cardiovascular; hazard ratio [HR], 1.21; 95% CI, 1.02 to 1.44); they also had fewer nonfatal MI (HR, 0.79; 95% CI, 0.66 to 0.95).

The effects continued throughout the follow-up period, with HR for death 1.19 (95% CI, 1.03 to 1.38) and HR for nonfatal MI 0.82 (95% CI, 0.70 to 0.96).

The authors conclude that in this high-risk study population with a history of long-standing, poorly controlled diabetes, intensive blood glucose control with a target HbA1c <6.0% did not significantly reduce major cardiovascular events up to 5 years, but was associated with increased mortality risk. They discuss the implications of their results, commenting that they apply only to patients similar to those in the trial; they note that another study in newly diagnosed patients found significant improvements in cardiovascular outcomes at 20 years with intensive control (median achieved HbA1c 7.0%).