Despite robust evidence linking long-term hyperglycemia with cardiovascular complications, several large randomized trials found only modest benefits from intensive compared to standard glucose control. Of these trials, the Veteran Affairs Diabetes Trial (VADT), offers a unique long-term perspective in that there were analyses of outcomes at the end of the intervention trial, 5-years post-trial, and after 10-years post-trial. From the VADT and other large trials, we draw several valuable lessons that are relevant to the care of patients with type 2 diabetes. Intensive glucose control reduces development of nephropathy and retinopathy but not neuropathy, though evaluations of neuropathy are less consistent and conclusions regarding outcomes less reliable. While the VADT did not demonstrate reduction in cardiovascular outcomes at completion of the glucose lowering intervention, it did demonstrate a 17% reduction 5-years post-trial, which waned by 10-years post-trial observation. Of interest, the 5-year post trial period included 3 additional years of HbA1c separation between treatment groups which suggests that longer-term glucose control may be needed before benefits are seen. Other factors including hypoglycemia and increased glucose variation are also associated with cardiovascular events and are more prevalent during intensive glucose control, potentially lessening the benefit of lowering average glucose levels. Finally, intensive glucose control requires substantial effort from both the patient and clinician perspective. All of these factors must be kept in mind when considering the benefits of aggressive glucose control for each patient.
Keywords: Cardiovascular events; Diabetes mellitus; Glucose variability; Hypoglycemia; Intensive glucose control; VADT.