On September 23, 2010, the U.S. Food and Drug Administration (FDA) announced its decision to restrict the use of Avandia (rosiglitazone), a diabetes drug; specifically, only type II diabetics who are unable to control their condition with other medications are now eligible to take Avandia.1 This new regulation sprung from a 3-year reevaluation of Avandia’s safety by the FDA, which became necessary after Ohio Cardiologist Dr. Steven E. Nissen published a study in The New England Journal of Medicine linking Avandia to increased risk of adverse cardiovascular (ischemic) effects.
Through a meta-analysis of controlled studies by GlaxoSmithKline,2 the manufacturer of Avandia, Dr. Nissen found that use of Avandia, when compared with placebo or standard diabetes drugs, significantly increases heart attack risk and increases risk of death from cardiovascular causes. Intended for use in tandem with an appropriate diet and exercise program for type II diabetics, Avandia works by increasing a person’s sensitivity to insulin; it does not cure diabetes, but helps control blood sugar. One of Avandia’s side effects is fluid retention, which can cause or worsen congestive heart failure, resulting in symptoms like angina. This effect is particularly alarming since cardiovascular disease is the leading cause of death in type II diabetics and Avandia is so widely prescribed; according to the Washington Post, revenue from Avandia reached $2.2 billion in 2006.
Prior to publishing the study, Dr. Nissen had met with GlaxoSmithKline to review the safety information at issue. While one of the GlaxoSmithKline executives stated that the studies Dr. Nissen had analyzed did not demonstrate any impact of Avandia on cardiac death rates, Dr. Nissen had found a 64 percent increased risk. And, although GlaxoSmithKline publicly discredited the doctor’s analysis, scientists at GlaxoSmithKline had concluded that the doctor’s study was sound, according to internal documents.
The suspicion that GlaxoSmithKline knew of Avantia’s risks led to a 2-year Congressional investigation. In February 2010, the Senate Finance Committee released a 334 page report with findings that GlaxoSmithKline knew of increased cardiovascular risks, but attempted keep this knowledge from the public. In a press release surrounding the report, Senator Max Baucus voiced concerns that drug companies like GlaxoSmithKline abuse patient trust and responsibilities to patients by not telling the public about serious health risks associated with certain drugs.
The Finance Committee also found that, despite safety concerns voiced by its officials, the FDA permitted GlaxoSmithKline to continue conducting an “unethical and exploitative” Avandia clinical trial (TIDE). The Senate Committee wrote a letter to the FDA asking the agency to explain what steps it had taken to protect patients in the TIDE trial. After 2 advisory committee meetings, in 2007 and 2010, the FDA finally decided to increase warnings on rosiglitazone labels and limit use due to concern about cardiovascular risk; the FDA did not remove Avandia from the market, as 12 of the 32 advisory committee members had voted to do, acknowledging the Avandia’s benefits in glycemic control. Senator Baucus publically applauded the FDA’s new Avandia regulations for their value in protecting patients and helping patients and doctors make “safe and informed decisions when choosing their medicines.”
Kudos to Dr. Nissen for standing up to the establishment and doing the right thing. All drugs carry some baggage, and some are riskier than others. The best bet is not to use a drug unless your life depends on it, especially Avandia (rosiglitazone). If avoiding diabetes medication is not an option,metforminis an alternative oral hypoglycemic with lesser risk of heart failure. The good news is that type II diabetes is totally curable with safer protocols like weight loss, committing to a regular, moderate exercise program, and controlling blood sugar through carbohydrate restriction. Working with a personal trainer or nutritionist can help make these lifestyle modifications part of a normal routine that beats taking a life-endangering drug.
1. Generally, once a drug receives FDA approval, practitioners can use it for any condition, not just the one for which it was designed.
2. GlaxoSmithKline has been required to publish clinical trial results online since 2004, following settlement of a lawsuit filed by New York Attorney General, Elliot Spitzer for failure to make public studies which showed a link between antidepressant use and suicidal behavior in children and teenagers (see http://www.gsk.com/research/clinical/clinicalreg.html to review company-funded research).
References and Resources:
- U.S. Food and Drug Administration (FDA) web site. “FDA significantly restricts access to the diabetes drug, Avandia,” Sept. 23, 2010.
- Harris, Gardiner. “New F.D.A. – Transparence and Flexibility,” New York TimesSept. 25, 2010.
- Harris, Gardiner. “A Face-Off on the Safety of a Drug for Diabetes,” New York TimesFeb. 23, 2010.
- Woodcock J, Sharfstein J and Hamburg M. “Regulatory Action on Rosiglitazone by the U.S. Food and Drug Administration,” New Eng. J. Med. Sept. 23, 2010.
- Nissen SE, Wolski K. “Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes.” N Engl J Med 2007; 356:2457-2471.
- U.S. Senate Committee on Finance web site. “Grassley, Baucus Release Committee Report on Avandia: Senators Express Concern About FDA’s Role in Protecting Patients in Ongoing Avandia Study.” Feb. 20, 2010.
- The United States Senate Committee on Finance web site. “Baucus Applauds FDA Avandia Decision.” Sept. 23, 2010.
- U.S. National Library of Medicine web site: Pub Med Health. “Rosiglitazone,” Feb 22, 2010.
- U.S. National Library of Medicine web site: Pub Med Health. “Metformin,” July 1, 2010.
- Associated Press. “Senate Report Ties GlaxoSmithKline Diabetes Drug Avandia to Heart Attack Risks,” Washington Post Feb. 21 2010.
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