Is tight glycemic control in type 2 diabetes really worthwhile?

Treating early gives the best benefits

Three trials, designed to look at whether near-normal glycemic control reduces cardiovascular disease in type 2 diabetes, have just been completed. These are the ACCORD,7 the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation),8 and the VADT (Veterans Affairs Diabetes Trial)9 studies. There are 2 big differences between these studies and the ones mentioned previously. First, these trials were all short (3.5 to 5 years). Second, the patient populations in these 3 trials were older, had had diabetes for longer (eg, an average of 10 years in the ACCORD study), and were at higher risk of cardiovascular events, compared with the DCCT and UKPDS studies in which the patient populations were younger or recently diagnosed.

All 3 trials were able to achieve sustained reductions in HbA_1c levels for the duration of the studies, something that was difficult to achieve in previous trials, particularly the UKPDS. The ADVANCE study showed a significant reduction in microvascular complications (14%, 95% confidence interval 3% to 23%) and a non-significant reduction in the macrovascular events. By choosing an HbA_1c target of 6.5%, there was a 21% reduction in new or worsening nephropathy. Neither the VADT nor the ADVANCE studies showed increased mortality or cardiovascular event rate; however, the ACCORD study, which attempted the most aggressive lowering of HbA_1c levels (targeting < 6% in 6 months), showed a slight increase in deaths—1.7% versus 1.1%. This was, however, less than the predicted rate (4%), and overall the cardiovascular event rates in the intensive and standard groups (6.9% and 10.6%, respectively) were much lower than expected. Moreover, a prespecified subanalysis in the ACCORD study showed that patients treated intensively who showed the greatest reduction in primary macrovascular end points were at earlier stages of disease, with lower baseline HbA_1c values and no known baseline vascular diseases.7 Likewise in the VADT study, those with the shortest duration of diabetes (< 15 years) benefited the most from intensive control.9

Don’t throw the baby out with the bathwater

From the trials cited above, we can see that tight glycemic control in type 2 diabetes, with HbA_1c target levels of less than 7%, reduces the microvascular complications of diabetes. It might also reduce macrovascular complications if initiated early, although it might take longer for the benefits to become evident. According to the Diabetes In Canada Evaluation (a study of diabetes care in primary practice),10 physicians have difficulty helping their patients to achieve HbA_1c target values of less than 7%. The “headlines” of the ACCORD trial might suggest, to some, that physicians can “relax” in treating diabetes to target. This might be “throwing the baby out with the bathwater.” As advocated in the 2008 Canadian Diabetes Association clinical practice guidelines,11 an HbA_1c value of less than 7% will reduce microvascular complications. To further reduce the risk of nephropathy, an HbA_1c value of less than 6.5% is beneficial. In terms of reducing macrovascular disease, the most worthwhile approach is to target an HbA_1c value of less than 7% and begin a multifaceted cardiovascular risk-reduction approach as early as possible.