September 2007

A panel of medical experts has recommended keeping a controversial diabetes drug on the market, but has strongly advised the U.S. Food and Drug Administration to slap on new safety warnings.

The endorsement came in July after David Graham, the FDA scientist who publicized problems with Vioxx long before it was recalled, argued that Avandia should be pulled from the shelves.

"If rosiglitazone increases the cardiovascular risks, a wrong decision will cost thousands of lives," Graham says. He argues that there's no proof that Avandia provides "major" health benefits.

But a joint panel of experts -- convened after a May study in the New England Journal of Medicine found people who took the drug had as much as a 43 per cent higher risk of heart attacks -- voted 22 to 1 to keep it on the market with warnings, saying the benefits outweigh the risks. While the FDA often follows the advice of its advisory panels, it is not required to do so.

More than a million prescriptions for Avandia are filled in Canada every year. The drug, manufactured by GlaxoSmithKline, is used to treat insulin resistance. People with type 2 diabetes produce insulin but their pancreas either does not produce enough or their bodies do not use it effectively. More than two million Canadians have diabetes, 90 per cent diagnosed with type 2, which can lead to other medical problems, including heart disease, kidney failure, blindness and amputation.

GlaxoSmithKline argues that there is no increased risk, citing its own analyses of studies of Avandia.

"The number of myocardial infarctions is small, the data are inconsistent and there is no overall evidence rosiglitazone is different from any other oral anti-diabetes agents," says Dr. Ronald Krall, the company's chief medical officer.

The members of the FDA's Endocrine and Metabolic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee recommend safety warnings for certain diabetics, says Dr. Clifford Rosen. acting committee chair. There is a clear cut risk for subgroups of type 2 patients, including people who had -- or are at risk of having -- congestive heart failure or significant heart disease, especially those who have been treated in hospital, says Rosen, who is not with the FDA.

People who are taking nitrate medications and those who have used insulin injections for a number of years are also at greater risk, he says. "These are the people that clinicians are going to have to think twice about before prescribing the medication."

Dr. Douglas Throckmorton, deputy director of the Center for Drug Evaluation and Research, says the FDA will examine the recommendations of the advisory committees. The agency could give Avandia a prominent black box warning, the most serious, or just provide a list of risks and contraindications.

"Obviously this is a high priority for this centre, we want to move this forward as quickly as we can," he says.

Canadians will have to wait for Health Canada to make a decision.

Dr. Lawrence Leiter, head of the division of endocrinology at St. Michael's Hospital, says the advisory panel's recommendation highlights the fact that it is still an effective agent to lower blood sugar. It was the appropriate decision given the confusing and conflicting data about the drug and its possible health problems, he says, adding larger, better-designed studies are currently underway with results expected within one or two years.

The diabetes drug Metformin is often the first used to treat type 2 diabetes, while thiazolidenediones, which include Avandia and Actos, are considered second-line drugs, according to current Canadian Diabetes Association guidelines. Each drug comes with its own set of advantages and disadvantages and are prescribed on a case-by-case basis.

Leiter says Avandia remains an important drug in the arsenal to treat type 2 diabetes as the disease reaches epidemic proportions. "We wouldn't wish to lose one of our more effective medications."

A Health Canada spokesperson, earlier this year, was reported as saying that the agency is "actively reviewing" the research and that it recommends diabetics consult with their doctors before deciding to stop taking Avandia.

-- Metroland Newswire