Whether glycaemic control may result in a reduction of cardiovascular (CV) risk has been a matter of continuous discussion
and investigation. Epidemiological analyses have extensively suggested a relationship between glycaemic control and CV events;
however, the results of intervention trials have been less conclusive. The UKPDS reported a 16% reduction in the risk of myocardial
infarction, but this reduction was not statistically significant. The results of the Kumamoto and PROactive studies could
not allow any firm conclusions to be drawn either, because of limited size and the defined primary endpoint, respectively.
The results of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) and Action in Diabetes and Vascular Disease:
Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trials and the Veteran Administration Diabetes Trial
(VADT) were published in rapid succession over the second half of 2008 and at the beginning of 2009. A total number of almost
25,000 type 2 diabetic patients were recruited in these three trials, which assessed the effect of intensive glycaemic control
vs conventional treatment on well-defined CV endpoints. In spite of the achievement and maintenance of strict glycaemic control
(HbA
1c <7.0%), no beneficial effect of intensive therapy was apparent in any of the studies. At the same time these results were
presented, the results of an analysis of the 10 year follow-up of the UKPDS also became available and provided a more optimistic
view of the potential benefit of achieving good glycaemic control. The relative risk reductions for myocardial infarction
and all-cause mortality were significantly lower in the patients who initially received the intensive treatment compared with
those in the conventional treatment arm. Moreover, the initial benefit in terms of microvascular complications observed at
the end of the intervention trial remained unaltered at follow-up. Once again the debate on the importance of glycaemic control
in preventing macrovascular complications remains unsettled. These results, however, require some reconciliation, and the
objective of this commentary is to analyse a series of elements, including the changes in the treatment approach to CV risk
factors in type 2 diabetes, the effect of glucose-lowering agents, and the characteristics of the patients included in the
different trials, that should be taken into account when interpreting the results of intervention trials in type 2 diabetes.
Keywords Cardiovascular disease - Clinical trials - Diabetic complications - Disease duration - Macrovascular complications - Microvascular complications - Risk of hypoglycaemia - Type 2 diabetes - Type 2 diabetes treatment