Clinical trial designs for diabetes drugs are not good enough at detecting cardiovascular risk with GlaxoSmithKline’s (GSK) Avandia being Exhibit A, according to experts at a Tuesday meeting of CDER’s Endocrinologic and Metabolic Drugs Advisory Committee.
The FDA recently sent GSK a warning letter for not reporting several postmarketing studies testing Avandia (rosiglitazone maleate), which is a Type 2 diabetes treatment. The drug’s sales have plummeted due to safety concerns. But the problem goes beyond Avandia, the experts said.
The FDA’s current “glucose-centric” regulatory approach to developing diabetes drugs is deeply flawed, Steve Nissen, medical director of the Cleveland Clinic’s Cardiovascular Coordinating Center, said.
“The goal of merely lowering blood glucose levels is too simplistic,” he said. “We must reduce the complications of diabetes, including cardiovascular effects.”
FDA policy hinders that goal. “Absence of information on the macrovascular effects of diabetes therapies is the unfortunate consequence of a regulatory policy that emphasizes the importance of glucose lowering, not health outcomes, as the therapeutic goal,” he said.
The National Heart and Lung Blood Institute’s Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial “demonstrated that a drug regimen designed to lower blood glucose is capable of increasing mortality in diabetic patients,” Nissen added. “Multiple rosiglitazone meta-analyses of cardiovascular outcomes showed improved glycemic control but an increase in myocardial ischemic mortality.”