Diabetes is associated with a reduced lifespan, largely as a consequence of cardiovascular disease. 1-3 Although diabetes significantly increases the risk of cardiovascular events, 1 the relative increase in events for each percent increase in glycated hemoglobin is modest. 4 Microvascular complications of diabetes remain the leading causes of blindness and renal failure in the developed world and are much more closely associated with hyperglycemia than with macrovascular complications. 4

Though there is a link between hyperglycemia and cardiovascular risk, there is less evidence that glucose lowering is associated with reduction in risk. Patients with type 2 diabetes whose glycated hemoglobin levels were reduced from 8 to 7% in the United Kingdom Prospective Diabetes Study (UKPDS) did not exhibit a reduction in cardiovascular events, although a subgroup of patients treated with metformin had a lower risk of cardiovascular events. 5 Among patients with type 1 diabetes studied in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC), glucose lowering was associated with a long-term benefit with regard to cardiovascular complications that became apparent only years after recruitment. 6 Two studies in this issue of the Journal—the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial7 (ClinicalTrials. gov number, NCT00000620) and the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation) trial8—sought to determine the effect of the lowering of glucose to near-normal levels on cardiovascular risk. Although the ACCORD and ADVANCE trials both compared intensive and standard glucose-lowering targets in type 2 diabetes, the trials differed substantially (Table 1).