The controversial diabetes drug Avandia should stay on the market for now, with relaxed restrictions on its use, Food and Drug Administration advisers said on Thursday.
The FDA has been reconsidering its approval of Avandia, which was the world’s No. 1 diabetes drug until research showed it could raise the risk of heart attacks and other heart dangers. Since then, its use has been heavily restricted and prescriptions have plummeted, and the FDA wanted to know if it was worth even keeping the drug on the market.
The agency’s expert panel of advisers said the data is clearly confusing and they were deeply divided at the end of two days of hearings on the issue. Most voted to modify the restrictions on Avandia’s use, but not to lift them completely. The FDA usually follows the advice of its panels.
Avandia, known generically as rosiglitazone, is in a relatively new class of drugs aimed at helping the body's natural insulin work better. In May 2007, Dr. Steve Nissen of the Cleveland Clinic issued an analysis of other studies that suggested Avandia raised the risk of heart attack by 43 percent. His report in the New England Journal of Medicine set off a storm of controversy, as doctors and regulators struggled to balance the potential risks of the drug versus its benefits in treating millions of people with diabetes.
European regulators removed Avandia from the market in 2010 and the FDA severely restricted its use in the United States. FDA ordered an outside review of the clinical trial run by GlaxoSmithKline, which makes Avandia. The panel was considering the results of the review in its meeting this week.
Most of the panelists voted to keep the special restrictions in place, with some modifications. The restrictions require doctors who prescribe Avandia to undego special education about its risks. Patients who want to take the drug have to enroll in a special program, called the Rosiglitazone Risk Evaluation and Mitigation Strategy (REMS), to get the drug.
Rebecca Killion, a patient representative on the committee from Bowie, Md., argued for keeping the drug available.
“What we fear overpowers what we know,” she said. “One of the things that we can’t know is what is the harm to patients that might not have access to a therapy that is best suited to them.”
The restrictions have limited who gets Avandia, says FDA's Joyce Weaver. She told the panel that prescriptions have dropped from a peak of more than 64,000 a month to 1,066 a month this year.
The expert panelists said they were worried that dropping too many of the restrictions would lead to more doctors prescribing the drug for people who already have a high risk of heart disease and who shouldn't take it. FDA's Dr. John Jenkins agreed that was a risk. "Too often at these meetings we hear from providers who say 'I don't read the label,'" Jenkins said.
Type-2 diabetes is caused as the body gradually loses its ability to respond to insulin, a condition called insulin resistance. Overeating, a lack of exercise, genes and other factors all play a role. More than 24 million Americans have type-2 diabetes.
Diet and exercise can control milder forms of diabetes but there are dozens of drugs on the market for people who need more help, including the sulfonylureas, biguanides,alpha-glucosidase inhibitors, meglitinides, dipeptidyl peptidase IV (DPP-IV) inhibitors, and thiazolidinediones -- the class that includes Avandia. Patients with severe diabetes must inject insulin.
Untreated, diabetes can damage the eyes, kidneys and other organs, and can damage blood vessels in the extremities, forcing amputation of toes, feet and even the legs.