GSK drug's safety questioned

A prominent US clinician has concluded that a diabetes drug produced by UK pharmaceutical company GlaxoSmithKline (GSK) increases the risks of heart attack and death. 

Steven Nissen from the Cleveland Clinic, Ohio, undertook a meta-analysis of clinical studies comparing patients treated with GSK’s Avandia (rosiglitazone maleate) with controls. He concluded that Avandia was associated with a 43 per cent increase in the risk of heart attack. His article, published in the 14 June edition of the New England Journal of Medicine (NEJM), was released early by the journal’s editors due to its public health concern. 

Avandia is one of the most commonly-prescribed drugs for type two diabetes - a condition caused by the body’s resistance to insulin. This leads to elevated blood sugar, which has a number of long-term health risks including kidney failure, blindness and cardiovascular disease. Avandia increases the body’s sensitivity to insulin and stimulates cell metabolism to reduce the level of sugar in the blood.

Nissen analysed studies involving a total of nearly 28 000 patients: 15 560 people took the drug, while 12 263 controls did not. In the group taking Avandia, there were 86 heart attacks compared with 72 in the control group. The total number of deaths from heart disease was also higher: 39 among people who took the drug compared with 22 in the control group. Although the number of heart attacks and deaths in each group was only a few dozen out of many thousand, Nissen cautioned that this significant increase in heart disease in such a high-risk group, associated with such a widely-prescribed drug, was ’worrisome’. 

GSK seized upon the limitations of a meta-analysis of short-term studies, releasing a statement saying that the company ’strongly disagreed with the conclusions reached in the NEJM article, which are based on incomplete evidence and a methodology that the author admits has significant limitations.’ Nevertheless, GSK’s share price fell by five per cent on 21 May, and has continued to fall the following day.

Regulation concerns

The US Food and Drug Administration (FDA) also faced criticism for its lack of regulatory control, and released a safety alert in response to the study, pointing to its ongoing scrutiny of the safety of Avandia. 

’In this case, the FDA is carefully weighing several complex sources of data, some of which show conflicting results, related to the risk of heart attack and heart-related deaths in patients treated with Avandia,’ said Steven Galson, director of the FDA’s Centre for Drug Evaluation and Research. ’We will take the issue of cardiovascular risk associated with Avandia and other drugs in this class to an Advisory Committee as soon as one can be convened.’

Nissen, recently voted one of Time magazine’s 100 most influential people, has previously been vocal in his criticism of the FDA. Earlier this year he testified before a US Congress House Commerce subcommittee. He accused the agency of ignoring evidence that drugs were unsafe and succumbing to pressure from drug companies to approve them. 

Having recently received a vote of confidence from Congress in the form of the FDA revitalisation act, the agency was keen to draw attention to the fact that Avandia’s labelling had been updated on several occasions to reflect new safety data. ’The most recent labelling change [in 2006] included a new warning about a potential increase in heart attacks and heart-related chest pain in some individuals using Avandia. This was based on the result of a controlled clinical trial in patients with existing congestive heart failure.’

The FDA is yet to confirm a date for an advisory committee hearing, when all of this data will come under further scrutiny. 

Victoria Gill

Enjoy this story? Spread the word using the ’tools’ menu on the left.