Is tight glycemic control in type 2 diabetes really worthwhile? Yes.

S ince the first big landmark trial on glycemic control and complications in type 1 diabetes (DCCT [Diabetes Control and Complications Trial]) 1 was published in 1993, almost every major trial for type 1 and type 2 diabetes has consistently demonstrated the beneficial effects of lowering glucose on diabetes complications. According to large randomized trials, there is no question that the lower the hemoglobin A 1c (HbA 1c) levels, the lower the risk of microvascular disease. 2 The relationship between macrovascular disease and increased glycemia has been shown in many epidemio-logic studies, including the epidemiologic analysis of the relationship between HbA 1c and vascular disease in the UKPDS (United Kingdom Prospective Diabetes Study). 4 trial, the 10-year posttrial monitoring of the DCCT, showed a 40% reduction in cardiovascular events and an almost 60% reduction in myocardial infarction (MI), stroke, and cardiovascular death in those patients who were, initially, intensively controlled compared with those less intensively controlled, even though their HbA 1c values were the same at the end of the trial. (Although this study involved individuals with type 1 diabetes, it is in a sense a better demonstration of the singular effect of glucose lowering on macrovascular disease without the other confounding vascular risk factors found more frequently in type 2 diabetes.) Original data from the UKPDS, which included subjects with type 2 diabetes, showed a significant 25% reduction in microvascular complications (P = .0099) and a non-significant 16% reduction in MI (P = .052). In addition, the UKPDS's 10-year follow-up 5 continued to show a reduction in microvascular complications, despite similar HbA 1c values between the intensive and control groups, during most of the posttrial period. There was also a significant reduction in MI (15%, P = .01) and death from any cause in the sulfonylurea insulin–treated group (13%, P = .007) and MI (33%, P = .005) and death from any cause (27%, P = .002) in the Metformin-treated group. The implication is that tight glycemic control in newly diagnosed diabetes patients has a lasting effect on the reduction of both microvascular and macrovascu-lar complications. This is the case even if glycemia increases over time. The same " legacy " effect seen in the EDIC trial and the UKPDS follow-up has also been demonstrated in the Steno-2 Study. 6 This 8-year trial of a multifactorial risk-reduction strategy, including a target HbA 1c value of 6.5%, clearly showed reduced …