The Veterans Affairs Cooperative Studies Program (VACSP) has just initiated a trial of the effect of intensive glucose control on cardiovascular complications in patients with type 2 diabetes. The name of the trial is “VACSP #465, Glycemic Control and Complications in Diabetes Mellitus type 2” (V.A. Diabetes Trial [VADT]). The trial is expected to generate discussion in the diabetes community because the central role of glucose control in preventing or delaying long-term complications is generally accepted. The data on macrovascular disease are not yet conclusive. The VADT is directed at type 2 diabetic patients with established uncontrolled diabetes. This is the population most frequently encountered by the practicing physician. Cardiovascular (CV) complications are the major causes of morbidity and mortality in patients with type 2 diabetes (1). Efforts to reduce glucose levels in these patients must be balanced between risks and benefits. Consideration of intensive therapy must include effects of glucose control on microvascular complications, macrovascular complications, complications of therapy, and socioeconomic issues, including patient quality of life, compliance with therapy, and distribution of available funds for care of patients with diabetes. ### Microvascular disease Both the Diabetes Control and Complications Trial (DCCT) (type 1 diabetes) and the UK Prospective Diabetes Study (UKPDS) (new-onset type 2 diabetes) showed a significant beneficial effect of glucose control on microvascular complications (2,3), as did the smaller Kumamoto study (4). Basic biochemical and animal studies provide a solid foundation for these findings, as do epidemiological studies. From a clinical standpoint, this issue is more complicated. Risk-to-benefit ratios must be considered. This has not been adequately addressed in older established patients with type 2 diabetes. In the UKPDS the main effect of glucose control after 10.5 years was a 3/1,000 reduction in photocoagulation for retinal disease (from 1.1% in the standard arm to 0.8% in the …