Cardiovascular disease is the leading cause of death in patients with Type 2 diabetes, accounting for approximately 70% of all mortality in people with diabetes. People with diabetes are twice as likely to suffer heart disease or experience a stroke compared to their non-diabetic counterparts. Diabetics also tend to develop heart disease and have strokes at an earlier age than their peers. Additionally, heart attacks in diabetics generally cause more damage than in non-diabetics and are more likely to result in death.
Since patients with Type 2 diabetes face a higher risk of cardiovascular disease, diabetic specialists and their patients were shocked when a study published in the May 21, 2007 issue of the New England Journal of Medicine (NEJM) revealed that the leading diabetes drug, Avandia, is associated with a 43% increase in heart attacks and up to a 64% increase in cardiovascular deaths.
Experts say the new study findings are especially alarming because two-thirds of the people with Type 2 diabetes die of heart problems. In a May 21, 2007 letter to GlaxoSmithKline, the manufacturer of Avandia, US Senators Max Baucus (Chairman of the Senate Committee on Finance) and Chuck Grassley (Ranking Member of the Senate Committee on Finance) wrote:
“It is troubling, to say the least, that by taking Avandia, diabetics may be increasing their risk of the very adverse event that they hope to prevent by controlling their blood sugar.”
Even more worrisome, medical experts point out that the studies analyzed in the NEJM report – some lasting as little as 24 weeks – were not designed to look for heart risks and it may be that higher risks will appear after a longer term of use. Dr. David Nathan, Chief of Diabetes Care at Massachusetts General Hospital, who reviewed the paper for the NEJM, told the Associated Press, “This analysis is just scratching the surface of what may be there.”
Major Failure of Drug Approval Process
Avandia (rosiglitazone) was approved by the FDA in 1999 for the treatment of Type 2 diabetes, a disease that affects between 18 to 20 million Americans. Following regulatory approval Avandia was promoted as being safer than Rezulin, a diabetes drug removed from the market in 2000 after patients taking the drug developed liver damage.
Avandia is currently the top-selling diabetes drug with total US sales of $2.2 billion in 2006, according to IMS Health, a healthcare tracking information firm. A one-month supply sells for between $90 and $170, the Associated Press reported on May 23, 2007.
In an editorial accompanying the NEJM study, Dr. Bruce Psaty of the University of Washington and Dr. Furberg of Wake Forest University wrote that the drug “…represents a major failure of the drug-use and drug-approval processes in the United States.” They also state, “…the rationale for prescribing rosiglitazone at this time is unclear,” because when the drug was approved its benefits were “at best mixed.”
Warnings Ignored for Years
Documents dating back 7 years show that the FDA knew about the risks associated with Avandia yet did little to protect consumers. The day after the new study appeared online, on May 23, 2007, Dr. Sidney Wolfe, director of Public Citizen, a non-profit health research group, sent a letter to FDA Commissioner Andrew von Eschenbach, which described a July 16, 2002 FDA memo that showed FDA scientists had recommended that the label for Avandia be amended to include post-marketing reports of heart failure among patients taking the drug.
“The failure of the FDA to act on the recommendations made almost five years ago by its Division of Drug Risk Evaluation is yet another case in which the conclusions of scientists who are engaged in post-market drug safety review are not taken seriously enough or addressed soon enough,” Dr. Wolfe said in a press release.
“As a result,” he stated further, “millions of people – to the detriment of their health – are prescribed drugs whose risks are dangerously understated, instead of being prescribed safer, equally, or more effective alternative drugs.”
New Details Deepen Concerns
Following the NEJM paper a new study has revealed additional details on the side effects of Avandia indicating that the drug causes 50% greater weight gain than similar medications while doubling the risk of dangerous fluid retention in the body.
In the new study, a team of researchers led by Bernd Richter at Heinrich Heine University in Dusseldorf, Germany, reviewed 18 previous studies involving 8,000 patients. They found the risk of dangerous fluid retention in the body – edema – doubled in those taking the Avandia, compared with patients on other diabetes medications. The diabetics taking Avandia had a 7% risk of edema – five times higher than those taking placebos.
Edema is characterized by swelling of the ankles and legs, but can lead to more than just discomfort. Richter explains that the extra fluid in the body can create more work for the heart, causing a shortness of breath and possibly heart failure.
His team’s analysis also showed that patients receiving Avandia gained 50% more weight, on average, than their counterparts on other diabetes medications (2.1 kilograms compared with 1.4 kg).
These new findings, added to the earlier results suggesting the increased risk of heart attack and bone fractures with Avandia, should be a matter of concern, says Richter, adding that it is unclear exactly why the drug would cause complications such as edema: “Nobody knows exactly why this happens.” Richter believes that the short-term results he analyzed in his review offer enough reason to reduce the widespread use of Avandia. “We don’t have long-term data, and in the meantime the public takes part in a large-scale experiment.”
1. Philip D. Home, D.M., D.Phil., Stuart J. Pocock, Ph.D., et.al, for the RECORD Study Group.Rosiglitazone Evaluated for Cardiovascular Outcomes – An Interim Analysis. N EnglJ Med 2007;357 Vol 357:28-38.
2. Richter B, Bandeira-Echtler E, Bergerhoff K, Clar C, Ebrahim SH. Rosiglitazone for type 2 diabetes mellitus. Cochrane Database of Systematic Reviews 2006, Issue 2. Art. No.: CD006063. DOI: 10.1002/14651858.CD006063. pub2. First published online: April 19. 2006.