Regulators in the European Union (EU) have suspended the sale of GlaxoSmithKline's (GSK) highly controversial diabetes blockbuster drug Avandia, while the US have imposed severe restrictions on concerns that the drug increased the risk of heart attacks in diabetic patients.

With both regulators yesterday announcing their individual regulatory decisions, the EU regulator the European Medicines Agency (EMA) suspended marketing authorisation for all rosiglitazone-containing drugs including Avandia and said that drug will be pulled from Europe within the next few months.

The US regulator the Food and Drug Administration (FDA) severely limited access to the drug. Patients in the US, who are under Avandia can continue taking the drug but will have to sign a consent statement acknowledging that they understand all the risks before they can buy the prescribed drug.

Doctors cannot prescribe Avandia to new patients unless they certify that they have exhausted all other remedies to control their blood sugar levels including Avandia's main competitor, Actos, made by Japanese drugmaker Takeda Pharmecuticals.

''Data from clinical trials, observational studies and meta-analyses of existing studies that have become available over the last three years have suggested a possibly increased risk of ischaemic heart disease associated with the use of rosiglitazone. Further restrictions on the use of these medicines in patients with ischaemic heart disease were introduced,'' said the EMA in a statement.

''The availability of recent studies has added to the knowledge about rosiglitazone and overall, the accumulated data support an increased cardiovascular risk of rosiglitazone. In view of the restrictions already in place on the use of rosiglitazone, the committee could not identify additional measures that would reduce the cardiovascular risk.

The committee therefore concluded that the benefits of rosiglitazone no longer outweigh its risks and recommended the suspension of the marketing authorisation of the medicines,'' it added.

With the EMA pulling out the drug from Europe and the FDA imposing such severe restrictions basically kills Avandia, which was GSK's blockbuster drug until the side effects of the drug came into public domain that led to shrinking global sales of the pill from $3.2 billion in 2006 to $1.19 billion last year.

In a statement put out by GSK after the rulings, the company said that although it continues to believe that Avandia is an important treatment for patients with type 2 diabetes, it will voluntarily cease promotion of the drug in all the countries in which it operates.

The FDA has also ordered GSK to end a controversial study TIDE comparing Avandia and Actos, as well as to conduct an independent assessment of the Record trial, a landmark study of Avandia's heart effects, that was published in mid-2009 by the respected medical journal The Lancet, which said that Avandia did not pose a serious heart attack risk.

Avandia was approved in 1999 to help diabetic patients control their blood sugar levels by making them more sensitive to their own insulin.

Shortly after launching Avandia in the market in 1999, SmithKline Beecham's research labs began a study to find out whether the drug was safer for the heart than Actos.

The findings showed that Avandia posed significant heart risks, but within a year of its internal research finding, US drug giant SmithKline Beecham merged with British drug giants Glaxo Wellcome in 2000 to form GlaxoSmithKline.

Although GSK is required in most cases by the US and other countries' laws to post the research results on its website or submit them to drug regulators, the merged entity chose to ignore the law.

GSK then spent the next 10 years trying to cover up the findings as putting a ''safety risk'' tag to the drug would have resulted in $600 million in lost sales from 2002 to 2004 alone. (See: GlaxoSmithKline: truth is a bitter pill) 

In May 2007, Steven Nissen, chair of cardiovascular medicine and medical director at Cleveland Clinic, published his findings on Avavdia in The New England Journal of Medicine that suggested that the drug increased the risk of heart attacks in diabetic patients.

GSK has already been bombarded with more than 13,000 lawsuits over Avavdia from users who allege that they had been misled about the drug's safety. In July 2010, the company paid $460 million to settle 10,000 of these claims.

In India although many doctors in areas have stopped prescribing the drug since its side effects became known in 2007, it is not the case in rural India, where doctors continue to prescribe rosiglitazone to diabetic patients.

India's National Pharmaco Vigilance Advisory Committee has to enlighten doctors in the country of the new ruling by regulators in the US and the EU.