GSK hid heart risks of diabetes drug, claims Senate committeeBMJ 2010; 340 doi: https://doi.org/10.1136/bmj.c1107 (Published 23 February 2010) Cite this as: BMJ 2010;340:c1107
The US Senate’s Finance Committee has claimed that GlaxoSmithKline (GSK) knew that “there were possible cardiac risks associated with Avandia” (rosiglitazone) for several years before a 2007 study in the New England Journal of Medicine showed a link between the drug and heart attacks.
The committee released a 342 page report on Saturday 20 February. It said the company should have warned patients and the Food and Drug Administration. “Instead,” the report says, “GSK executives attempted to intimidate independent physicians, focused on strategies to minimize or misrepresent findings that Avandia may increase cardiovascular risk, and sought ways to downplay findings that a competing drug might reduce cardiovascular risk.” It says that another drug, pioglitazone (Actos), might pose less risk to patients.
Rosiglitazone, a thiazolidinedione, is used to treat type 2 diabetes. It helps control blood sugar concentrations by increasing sensitivity to insulin. It is marketed in the United States as Avandia, Avandamet (with metformin), and Avandaryl (with glimepiride).
The 2007 study, a meta-analysis by Steven Nissen and Kathy Wolski of the Cleveland Clinic (New England Journal of Medicine 2007;356:2457-71, doi:10.1056/NEJMoa072761), concluded: “Rosiglitazone was associated with a significant increase in the risk of myocardial infarction and with an increase in the risk of death from cardiovascular causes that had borderline significance.”
Besides its report released on Saturday, the committee sent an accompanying statement and a 92 page document to the FDA commissioner, Margaret Hamburg. It described its investigation and findings and asked the FDA what it would do to protect patients in an ongoing clinical trial with rosiglitazone, called the thiazolidinedione intervention with Vitamin D evaluation (TIDE) study.
In an online press release GSK has criticised the Senate committee’s report and rejected its conclusions. It said the report’s conclusions about the safety of rosiglitazone were “based on analyses that are not consistent with the rigorous scientific evidence supporting the safety of the drug.” It said the report selectively picked information from documents “which mischaracterizes GlaxoSmithKline’s comprehensive efforts to research Avandia and communicate those findings to regulators, physicians, and patients. In fact, the safety and effectiveness of Avandia is well characterized in the label approved by the FDA.”
The company further said, “Contrary to the assertions in the report, and consistent with the FDA-approved labeling, the scientific evidence simply does not establish that Avandia increases cardiovascular ischemic risk or causes myocardial ischemic events.”
It said that the FDA had considered assertions by the FDA staff member David Graham that rosiglitazone increased the risk of heart attacks and should be withdrawn from the market. However, GSK said, the FDA followed the recommendation of an independent advisory committee and decided that the drug should remain available.
The FDA said it had told healthcare professionals and patients that it was reviewing primary data from a large study published last year (Lancet 2009;373:2125-35, doi:10.1016/S0140-6736(09)60953-3) and other studies. When the review is completed it will present “the totality of new and existing cardiovascular safety data on rosiglitazone at a joint public meeting of the Endocrinologic and Metabolic Drugs and Drug Safety and Risk Management Advisory Committees in July 2010” and would provide an updated assessment of risks and benefits of rosiglitazone in type 2 diabetes.
The Senate committee, which is chaired by the Democratic senator Max Baucus of Montana, has an interest in drug regulation and industry influence because it oversees government programmes such as Medicare for elderly people and Medicaid for poor people, which pay for medical care and many drugs.
The committee’s report was the result of two years of work by committee investigators, who looked at more than 250 000 pages of documents from, among others, GSK, the FDA, and the University of North Carolina, one of whose professors alleged he had been intimidated by GSK because he voiced concern about rosiglitazone (BMJ 2007;335:1113, doi:10.1136/bmj.39409.458611.DB). The company dismissed the suggestion when it was made in 2007 as “absolutely false.”
Senator Baucus said, “Americans have a right to know there are serious health risks associated with Avandia, and GlaxoSmithKline had a responsibility to tell them.”
Senator Charles Grassley of Iowa, the senior Republican on the committee, criticised the FDA because officials who study drugs already on the market report to “officials who approved the drug in the first place and have a natural interest in defending that decision.”
Cite this as: BMJ 2010;340:c1107