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Type 2 Diabetes: Major Trials Show Conflicting Results

Posted on: Friday, 13 June 2008, 09:00 CDT

Data from the ACCORD and ADVANCE trials have given conflicting messages on the suitability of intensive glycemic control in Type 2 diabetics. While the ACCORD intensive glycemic control arm was halted due to an increase in cardiovascular events, no significant increase or decrease in such events was shown in the ADVANCE trial. However, the full implications of these results are yet to be assessed.

According to data presented at the American Diabetes Association (ADA) conference in San Francisco, the intensive glycemic control arm of the ACCORD trial was discontinued in February 2008 as a result of 54 excess deaths, compared to the standard glucose control arm (257 versus 203). Nevertheless, the blood pressure and lipid lowering arms of the study are continuing, with all participants now assigned to the standard glucose control protocol.

Meanwhile, the ADVANCE trial found that intensive glucose control brought non-significant benefits in major macrovascular risk (6% relative risk reduction (RRR)) but significant improvements in microvascular health (21% RRR for diabetic nephropathy). The ADVANCE research team identified no subgroup within the trial population in which intensive diabetes control appeared to have a negative effect.

Both the ACCORD and ADVANCE trials were investigating the impact of tight glycemic control, intensive blood pressure and lipid profile management on the incidence of major cardiovascular events in Type 2 diabetics with a history of cardiovascular disease. The ADVANCE trial also investigated the impact on microvascular events such as nephropathy and retinopathy.

The results from both trials run counter to universal expectations of an improvement in cardiovascular risk through the tight glycemic control. Current opinion had expected target hemoglobin A1c levels, the accepted marker of three-month blood glucose levels, to tighten from 7% to 6.5% at some point in the near future.

Debate regarding the implications of the two trials is expected to be lively, with questions to be answered concerning the patient population in the ACCORD trial and the high degree of weight gain in the ACCORD trial compared to ADVANCE. It has been suggested that the data show that, in long-term Type 2 diabetes patients already at high risk of mortality owing to pre-existing cardiovascular disease, intensive glucose control may be "too little, too late" to cause statistically significant changes in the risk of future cardiovascular events. Alternatively, the benefits of intensive glucose control may not be apparent in the short-term in complicated, established Type 2 diabetes patients.

However, it may be some time before the implications of these results are realized. Indeed, as several physicians remarked at the ADA, it took 15 years of post-study follow-up to quantify a cardiovascular risk reduction for tight glycemic control in Type 1 diabetes.

Related research: Datamonitor, "Non-insulin antidiabetics" (DMHC2395) and "Insulin antidiabetics" (DMHC2394).

Source: Datamonitor

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