Clinical Health Updates

Intensive control of glucose does not improve T2DM outcomes (VADT)

Clinical Question:
Does intensive control of glucose improve outcomes in patients with type 2 diabetes?

Bottom Line:
Like the ACCORD and ADVANCE studies, this trial provides additional evidence that intensive glucose control does not improve outcomes in patients with type 2 diabetes mellitus. It is important to note that these patients had well-controlled hypertension (mean blood pressure = 126/68) and well-controlled hyperlipidemia (mean low-density lipoprotein = 80 mg/dL). (LOE = 1b)

Reference:
Duckworth W, Abraira C, Moritz T, et al, for the VADT Investigators. Glucose control and vascular complications in veterans with Type 2 diabetes. N Engl J Med 2009(2);360:129-139.

Study Design:
Randomized controlled trial (single-blinded)

Funding:
Industry + govt

Setting:
Outpatient (any)

Allocation:
Concealed

Summary:
The effects of intensive glucose control on cardiovascular events in patients with long-standing type 2 diabetes mellitus remain uncertain. The recent ACCORD (N Engl J Med 2008;358:2545) and ADVANCE (N Engl J Med 2008;358:2560) trials found that tight glucose control does not reduce the risk of macrovascular complications and may actually increase all-cause mortality in patients with type 2 diabetes mellitus. The authors randomly assigned 1791 military veterans (mean age, 60.4 years) who had a suboptimal response to therapy for type 2 diabetes to receive either intensive or standard glucose control. Other cardiovascular risk factors were treated uniformly. The mean number of years since the diagnosis of diabetes was 11.5, and 40% of the patients had already had a cardiovascular event. The goal in the intensive-therapy group was an absolute reduction of 1.5 percentage points in the glycated hemoglobin level, as compared with the standard-therapy group. The primary outcome was the time from randomization to the first occurrence of a major cardiovascular event, a composite of myocardial infarction, stroke, death from cardiovascular causes, congestive heart failure, surgery for vascular disease, inoperable coronary disease, and amputation for ischemic gangrene. The median follow-up was 5.6 years. Median glycated hemoglobin levels were 8.4% in the standard-therapy group and 6.9% in the intensive-therapy group. The primary outcome occurred in 264 patients in the standard-therapy group and 235 patients in the intensive-therapy group (hazard ratio in the intensive-therapy group, 0.88; 95% confidence interval [CI], 0.74 to 1.05; P=0.14). There was no significant difference between the two groups in any component of the primary outcome or in the rate of death from any cause (hazard ratio, 1.07; 95% CI, 0.81 to 1.42; P=0.62). No differences between the two groups were observed for microvascular complications. The rates of adverse events, predominantly hypoglycemia, were 17.6% in the standard-therapy group and 24.1% in the intensive-therapy group.