FDA wants closer scrutiny of new diabetes drugs
■ With type 2 diabetes already increasing heart risks, the FDA is seeking assurances that new drugs won't do further damage.
By Susan J. Landers — Posted Jan. 12, 2009
Washington -- The Food and Drug Administration is asking the manufacturers of new drugs and biologics for type 2 diabetes to be more diligent in determining if their therapies pose cardiovascular risks.
Until now, manufacturers had only to show that their drugs reduced blood sugar levels.
"We need to better understand the safety of new antidiabetic drugs," said Mary Parks, MD, director of the agency's Division of Metabolism and Endocrinology Products at the Center for Drug Evaluation and Research. She released a guidance document outlining the agency's recommendations for doing such an assessment Dec. 17, 2008.
More than 23 million people in the U.S. have been diagnosed with type 2 diabetes, which places them at a two- to four-times greater risk of heart disease than their nondiabetic counterparts. None of the currently approved antidiabetic therapies has been proven convincingly to reduce that risk, the FDA said.
The guidance, which is effective immediately, asks that phase II and III clinical trials demonstrate that new therapies do not increase cardiovascular risk in comparison with existing therapies.
The FDA also recommends to manufacturers that any cardiovascular events occurring in their trials be analyzed by committees of outside cardiologists.
The FDA already has placed black-box warnings on one class of type 2 diabetes drugs, thiazolidinediones, or TZDs, after they were found in postmarketing studies to increase the risk of heart failure. Two drugs, Avandia, or rosiglitazone, and Actos, or pioglitazone, are in that class.
Alarms about Avandia's association with increased heart risks were raised in a May 2007 New England Journal of Medicine article by Steven Nissen, MD, chair of Cleveland Clinic's Dept. of Cardiovascular Medicine. At the time, Dr. Nissen noted that because of this risk, Avandia is not a drug he recommends to patients.
GlaxoSmithKline, the manufacturer of Avandia, strongly disagreed with the conclusions in the NEJM article, faulting the authors' reliance on a meta-analysis rather than on long-term trials that Glaxo said showed no increased cardiovascular risk associated with Avandia.
Meanwhile, in a study published online Dec. 10, 2008, by the Canadian Medical Assn. Journal, researchers found that the risk of fractures doubled among older women who take TZDs for one year or more to control their diabetes.
"We knew going into this study there was an association between thiazolidinediones and fracture risk. However, the magnitude of the risk had not been evaluated," said Sonal Singh, MD, MPH, an assistant professor of internal medicine at Wake Forest University School of Medicine in Winston-Salem, N.C., and a co-researcher for the study.
Glaxo responded that the bone fracture risk had been reported previously and is noted on the Avandia label. A study to evaluate the effects of the drug on bone in women with type 2 diabetes is now enrolling participants, a spokesman said.
But in a commentary published online Dec. 10, 2008, in the CMA journal, Lorraine L. Lipscombe, MD, an adjunct researcher at the Institute for Clinical Evaluative Sciences in Toronto, recommended that TZDs not be considered a first-line therapy for type 2 diabetes.
"If a patient is unable to take other therapies or if other therapies have failed, there may be a role for thiazolidinediones in carefully selected patients duly informed of the potential adverse effects," she wrote.