Anti-diabetes drugs Avandia, Actos harmful to heart, says study

2 August, 2007:

Two drugs commonly prescribed to treat Type 2 diabetes have been found to double the risk of heart failure.

A study of data about over 78,000 patients suggests that GlaxoSmithKline Plc’s Avandia and Takeda Pharmaceutical Company’s Actos medicines double the risk of heart failure in diabetics.

The analysis of existing studies in the journal Diabetes Care projected that one in every 50 patients who takes Avandia or Actos over a 26-month period would be hospitalised for heart failure.

Heart failure, a condition in which the heart cannot pump enough blood, has already been identified as a risk of the two drugs.

The advisory committee of the United States Food and Drug Administration is meeting on July 30, 2007, to consider Avandia’s risk for heart attacks, a different disorder that gained public notice in May 2007 when a report in the New England Journal of Medicine linked Glaxo’s drug to a 43% increased risk of the complication.

Avandia and Actos already carry warnings of heart failure.

Yoon Loke, clinical pharmacologist of the University of East Anglia in Norwich, England and a co-author of the article, said: “We started this research because nobody could put an exact figure on the risk of heart failure.”

Avandia was the world’s largest-selling diabetes pill and London-based Glaxo’s second-biggest drug in 2006, fetching the company $3.3 billion. After the heart-attack risk was reported in May 2007, Avandia sales fell by 22% in the second quarter as Osaka-based Takeda’s Actos overtook it in the United States.

Avandia has heart-attack risks that will require restricting the drug’s use, Food and Drug Administration officials said in a report. The FDA’s advisory committee is not expected to consider action on Actos soon.

Jean-Pierre Garnier, chief executive officer of Glaxo, claimed that other new data on Avandia showed that the pill is safe. “The evidence is supportive of Avandia’s risk-benefit ratio and its effect on cardiovascular safety,” Garnier told a news conference on July 25, 2007. He added: “We stand firmly behind the safety profile of Avandia.”

The study report in Diabetes Care confirms earlier reports that treatment with Avandia and Actos increased the likelihood of heart failure, possibly by causing fluid retention or swelling, which can make the heart work harder. The study found that one-fourth of heart-failure cases occur in people younger than 60.

The research was completed in 2006 and the article submitted to the journal in January 2007. Diabetes Care, published by the American Diabetes Association, posted the study online on May 29, 2007, for its subscribers before distributing it on July 27, 2007, in the journal’s print edition.

The FDA changed patient information on Avandia in 2001 and on Actos by 2002 to warn that the medicines increased risks of heart failure in diabetics. Labels for both treatments in Europe say that they should not be given to people with heart failure or a history of the condition.

An estimated 246 million people, nearly 6% of the world’s adult population, suffer from diabetes and 3.8 million people a year die from it, according to the International Diabetes Federation.

The cells of diabetic patients do not properly use insulin, a hormone that turns blood sugar into energy. Avandia or Actos work by making diabetics more sensitive to the hormone insulin and have been taken by over 15 million patients since 1999.