Intensive blood sugar control is associated with increased mortality among type 2 diabetics in ACCORD
June 12, 2008 By Vijayalakshmi Kunadian MBBS MD MRCP 
New England Journal of Medicine: The results of the ACCORD study published recently demonstrate increased mortality in the intensive blood sugar control arm compared with standard therapy among type 2 diabetes patients.
Glycemic control is one of the main treatment strategies for the management of patients with type 2 diabetes. If left untreated, type 2 diabetes can lead to major cardiovascular problems including coronary artery disease and stroke in addition to the systemic complications that are associated with this condition. Previous studies have suggested that an increase in glycosylated hemoglobin by 1% can lead to increased risk of cardiovascular events, death and increased incidence of retinopathy and renal failure. Hence the investigators of the ACCORD trial determined if an intensive blood sugar control strategy would result in a significant reduction in the incidence of long-term cardiovascular events including cardiovascular death. This study was however, terminated early because of the increased incidence of mortality in the intensive glucose control arm at 3.5 years of follow-up.
The ACCORD (The Action to Control Cardiovascular Risk in diabetes Study Group) study, sponsored by the NHLBI is a randomized study consisting of 10,251 patients. Type 2 diabetic patients from 77 centers with a glycosylated Hb level >7.5% aged between 40 and 79 years were recruited for the study. Patients with serious hypoglycemic events, those with body mass index >45 and those with renal impairment (serum creatinine >1.5 mg/dl) were excluded from the study. Patients were randomly assigned to an intensive therapy group (to achieve glycosylated hemoglobin-Hb level <6%, n=5128) and a standard therapy group (to achieve glycosylated Hb level of 7-7.9%, n=5123). The primary endpoint consisted of a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes.
The mean age of study patients in both groups was 62.2±6.8 and around 38% of patients were women. At study entry the mean glycosylated Hb level was 8.3±1.1. Patients were treated with insulin (34.1% vs. 35.7%), metformin (59.7% vs. 60%), any sufonylurea (50.8% vs. 49.4%), and any thiozolidinedione (19.5% vs. 19.2%) for glycemic control.
In the intensive therapy group there was an increased incidence of hypoglycemia requiring medical assistance (10.5% vs. 3.5%, p<0.001), requiring any assistance (16.2% vs. 5.1%, p<0.001), any non-hypoglycemic serious adverse event (2.2% vs. 1.6%, p=0.03) and fluid retention (70.1% vs. 66.8%, p<0.001) compared with standard therapy group. More patients gained weight (27.8% vs. 14.1%, p<0.001) in the intensive therapy group. At 3.5 years, there was no significant difference in the overall primary outcome between the intensive and standard therapy groups [6.9% vs. 7.2%, HR 0.90 (0.78-1.04), p=0.16]. However, there was an increase in death from any cause [n=257 (5%) vs. n=203 (4%), HR 1.22 (1.01-1.46), p=0.04] and cardiovascular cause [2.6% vs. 1.8%, HR 1.35 (1.04-1.76), p=0.02] in the intensive therapy group. Although the overall primary endpoint continued to decrease (non-significantly) after about 3 years, the increase in mortality was observed 1-2 years following randomization. Non fatal myocardial infarction was more frequent in the standard therapy group compared with intensive group [4.6% vs. 3.6%, HR 0.76 (0.62-0.92), p=0.004]. There was no difference in the incidence of nonfatal stroke, fatal or nonfatal congestive heart failure between the two groups.
Although the exact mechanism of death among these patients is uncertain, the investigators conclude that intensive blood glucose control among type 2 diabetic patients for 3.5 years increased mortality and did not significantly reduce major cardiovascular events.