The Heartbreaking Story of Avandia

Is the FDA asleep at the wheel? Despite warnings from their own scientists that the diabetes medication Avandia has been associated with increased severe cardiovascular risk and death, the Agency recommended (in July 2007) that the drug stay on the market.

The FDA’s Office of Surveillance and Epidemiology (OSE) told US government health panelists who evaluated Avandia that the drug’s heart risks warranted its withdrawal. Dr. David Graham, the OSE’s associate director, estimated that between 1,600 and 2,500 unnecessary and avoidable deaths from heart attack and heart disease brought on by the drug would occur “for every month that [Avandia] stays on the market.”

Why wouldn’t the FDA move immediately to protect public safety? After all, other diabetes medications on the market don’t carry these risks.

Heartless Profiteering?

Avandia (generic name rosiglitazone) is part of a class of oral type 2 diabetes medications called thiazolidinediones, which help the body produce less blood sugar (glucose) and use insulin better. People with type 2 diabetes aren’t able to properly utilize insulin, which is needed to process glucose.

Avandia is manufactured by the pharmaceutical corporation Glaxo­Smith­Kline. Sales of the drug brought in about $748 million (CDN) between April and June 2007 and more than $1 billion for the same period in 2006. About one million Americans and 350,000 Canadians have used Avandia.

In May 2007 the New England Journal of Medicine published a meta-study that revealed a 43 percent higher risk for heart attack in diabetics taking Avandia, compared with those taking other diabetes medications or none at all. The lead researcher, Dr. Steve Nissen, noted that Avandia was associated with “a significant increase in the risk of myocardial infarction” [heart]. Nevertheless, on July 30 US government health advisors ruled that the risks did not merit removal of the drug from the market.

This is a story we’ve heard before–remember Vioxx?

Heartbeat Repeat

In 2004 the COX-2 inhibitor Vioxx (rofecoxib) was voluntarily withdrawn from the market by its manufacturer, Merck, in the wake of revelations that, like Avandia, its risks for “cardiovascular adverse events” (heart disease, heart attacks, and death) outweighed the drug’s benefits. The FDA was slow to respond to these risks and Merck downplayed them.

The FDA estimate of avoidable deaths from Vioxx (in the US alone) was 27,000, but the OSE’s Graham has estimated there were an additional 88,000 to 140,000 cases of serious coronary heart disease related to the use of the drug. A 2005 editorial in the Canadian Medical Association Journal castigated the FDA and Health Canada for “failing miserably” to “sound the alarm” on Vioxx because of the agencies’ “current emphasis on partnerships with industry.”

GlaxoSmithKline wasted no time in responding to the warning study about Avandia, issuing a statement that said, “There was no evidence of any increase in death from either cardiovascular causes or all causes,” although the report admits that the drug “was associated with an increased risk of heart failure.”

The FDA website’s fact sheet on Avandia also points to cardiac failure and other cardiac effects as potential adverse side effects, but it appears that, as with Vioxx, known risks are being ignored by our regulatory agencies–to the detriment of public safety. Ironically, in response to the Vioxx withdrawal, the FDA pledged in 2004 to step up its “pharmacovigilance” while monitoring the risk-to-benefit balance of approved drugs.

Heart of the Matter

Type 2 diabetes can be prevented and treated with lifestyle modifications, which include adopting a high-fibre, low-fat diet, choosing foods based on the glycemic index, monitoring cholesterol levels, and exercising regularly.

In the few clinical trials reported to date, a number of supplements and herbs to control diabetes have performed effectively–with none or few side effects–against placebo in humans. For more information on safe, natural approaches to preventing and treating diabetes, read the November issue of alive.