Intensive glucose-lowering therapy, defined as aiming for HbA1c levels below 7%, improves glycemic control among high-risk patients with type 2 diabetes mellitus (T2DM). However, it has no long-term effect on cardiovascular outcomes in this patient population, according to findings from the Veterans Administration Diabetes Trial (VADT).

VADT (NCT00032487) was designed to evaluate whether intensive control of blood glucose levels would reduce the risk of cardiovascular events compared with standard therapy among 1,791 patients with T2DM who were at high risk for cardiovascular disease (CVD). The primary outcome was a composite of cardiovascular events, including cardiovascular death, myocardial infarction (MI), congestive heart failure, and severe coronary artery disease (CAD); amputation for ischemia; and interventions for CAD and peripheral vascular disease.

Compared with other recent trials of standard versus intensive glycemic control such as ADVANCE and ACCORD, VADT enrolled patients with a longer duration of T2DM and more severe cardiovascular risk, said VADT Co-Chair William Duckworth, MD, Veterans Administration Medical Center, Phoenix, AZ. The VADT study population included mostly male (97%), older patients (mean age, 60 years) with high background cardiovascular risk. At baseline, the mean HbA1c was 9.5%. Patients tended to be obese (mean body mass index, 31 kg/m²), 72% of patients had high blood pressure (mean, 132/76 mm Hg), 50% had an abnormal lipid profile, and 40% had a history of MI, angina, bypass surgery, stroke, or transient ischemic events. In addition, 43% had diabetic neuropathy at baseline, and 62% had retinopathy.

After a median of 6 years, patients in the intensive-treatment arm had a lower HbA1c (6.9%) than those in the standard-treatment arm (8.4%). As expected, compared with standard therapy, intensive glucose control was more likely to lead to episodes of mild hypoglycemia (77.1% vs 93.4%; p=0.01) and severe hypoglycemia (9.7% vs 21.1%; p=0.01).

Despite differences in glucose control, there was no difference in the time to primary outcome between the two treatment groups (p=0.12). Moreover, compared with standard therapy, intensive glucose control had no affect on the risk of all-cause mortality (HR=1.065; p=0.67).

Interestingly, the VADT investigators found that patients with a shorter duration of T2DM were more likely to benefit from intensive therapy (p<0.0001). This suggests that the damage inflicted by many years of T2DM is too great for even intensive therapy to overcome, Dr. Duckworth said. However, if verified, these data support the use of intensive therapy early in the treatment of T2DM, he concluded.