A large-scale clinical study of diabetes treatments has found no evidence to link GlaxoSmithKline's type 2 diabetes drug Avandia
A large-scale clinical study of diabetes treatments has found no evidence to link GlaxoSmithKline’s type 2 diabetes drug Avandia (rosiglitazone) with increased risk of heart attacks - despite an earlier meta-analysis suggesting the opposite (see Chemistry World, July 2007, p16).
The Accord (Action to Control Cardiovascular Risk in Diabetes) study - sponsored by the US National Heart Lung and Blood Institute (NHLBI) - was originally designed to determine whether intensively lowering blood sugar would reduce the risk of cardiovascular events such as heart attack, stroke, or death from cardiovascular disease, specifically in people with type 2 diabetes who are at particularly high risk for a cardiovascular event.
It recruited 10,251 diabetes patients with additional cardiovascular risks, such as high blood pressure and cholesterol. The patients were randomly assigned one of two treatment regimens - one group had their blood sugar levels reduced to below current clinical recommendations, and the other received standard blood sugar management, which includes rosiglitazone and other medicines. But the intensive treatment part of the trial was stopped 18 months early after a review of the data showed that more patients receiving intensive management of their blood glucose had died. All patients in that section of the trial have now been reassigned to standard blood sugar control.
Following Avandia’s link to a higher risk of heart attack, Accord’s designers decided to mine their own data on the drug’s effects. ’Because of the recent concerns with rosiglitazone, our extensive analysis included a specific review to determine whether there was any link between this particular medication and the increased deaths. We found no link,’ said William Friedewald of Columbia University, who chairs Accord’s steering committee.
’These could be important findings if they can shed more light on how we improve the management of patients with diabetes,’ said GSK in a statement. The company’s sales of Avandia have plummeted since the controversy arose last year.
Interestingly, a parallel diabetes study known as Advance responded to the Accord findings by revealing that they had seen no sign of the link between intensive blood sugar reduction and cardiovascular events. The American Diabetes Association said that the conflicting results ’further magnify the uncertainty over whether intensive glucose control may harm some people with diabetes’.
Steven Nissen of the Cleveland Clinic in Ohio, who conducted the meta-analysis that raised the initial concerns about Avandia’s safety, told Chemistry World that the Accord data did not necessarily give Avandia a clean bill of health. ’It really didn’t compare Avandia to other treatments, so it’s not likely to be helpful,’ said Nissen. ’Diabetes drugs have never been studied in large, well-powered outcomes trials. This must change. If the FDA insists on approving drugs to lower blood sugar, they must require Phase IV outcome trials.’