Intensive drug treatment linked to extra deaths in people with type 2 diabetes

Aggressive control of blood sugar failed to reduce cardiovascular events in patients with type 2 diabetes in two large trials⇑. Worse, one of the trials reported a significant increase in deaths associated with aggressive drug treatment aimed at reducing glycated haemoglobin concentrations to below 6% (hazard ratio 1.22, 95% CI 1.01 to 1.46). The authors were unable to explain the extra deaths, which led to the early termination of the trial after only 3.5 years of follow-up. More hypoglycaemia, greater weight gain, the rapid fall in glycated haemoglobin, or the ultra low target may all have contributed to the unexpected result according to two linked editorials (p 2630, p 2633). The authors also explored the heavy use of rosiglitazone in patients treated intensively but found no evidence of a link between this drug and the extra deaths. Rosiglitazone has been associated with an increased risk of heart attack.

The trials each recruited more than 10 000 adults with longstanding type 2 diabetes. About a third of the participants had a history of vascular disease and the rest had one or more risk factors. In the second trial, patients treated intensively with gliclazide and other drugs to reduce their glycated haemoglobin to no more than 6.5% were less likely to develop nephropathy over five years than controls (4.1% (230/5571) v 5.2% (292/5569); 0.79, 0.66 to 0.93). The lower target had no effect on cardiovascular events.

Both linked editorials agree that targets for glycated haemoglobin should stay at 7% for now in high risk patients. Controlling hyperglycaemia still matters, but so does control of serum lipids and blood pressure. Fewer than one in 10 patients meet current recommended targets for all three.

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