Researchers at The Cleveland Clinic recently completed an analysis of clinical trials on muraglitazar (Pargluva), a new diabetes drug, finding that it doubles the risk of death, heart attack, and stroke.
The results appeared in Thursday’s Journal of the American Medical Association (JAMA). Because of the study’s potential impact on public health, the journal expedited the release of the study and published it along with an editorial.
The study’s lead author is Steven Nissen, M.D., Medical Director of the Cardiovascular Coordinating Center at The Cleveland Clinic, and a nationally recognized expert in intravascular ultrasound imaging.
Muraglitazar was developed by Bristol-Myers Squibb and Merck & Co. It was evaluated by an advisory committee of the Endocrine and Metabolic Diseases Division of the FDA on September 9, 2005. The committee voted eight to one recommending approval of the drug for use in the treatment of patients with Type 2 diabetes, the most common form of the disease.
Dr. Nissen and his co-authors analyzed the publicly available clinical trial data reviewed by the FDA Advisory Committee and found that the combined incidence of death, heart attack, and stroke was 2.23 times higher in patients treated with muraglitazar, compared with patients receiving either a placebo or the diabetes drug pioglitazone.
Heart disease is the leading cause of death in patients with diabetes, accounting for more than 80% of mortality in this group. “Muraglitazar carries an unacceptable risk of heart-related complications and should not be approved until more safety data are available,” Dr. Nissan said.
The study raises serious questions about the FDA approval system. The only heart specialist on the FDA panel of experts convened to consider the approval of muraglitazar recused himself because of a conflict of interest. In recent months, Congress has taken a heightened interest in how the FDA selects panel members for its advisory committees.
Catherine DeAngelis, JAMA’s Editor, agreed with Nissen’s call for further research and questioned why the FDA, the organization that is responsible for looking after the safety of the public, did not ask for additional testing prior to the drug’s approval.