REGULATORS are likely to expect stronger reassurances about the cardiovascular safety of new type 2 diabetes drugs in the wake of the rosiglitazone case, a reality which will slow new developments, warns a leading diabetes expert.

Professor Paul Zimmet, Director Emeritus of the Baker IDI Heart and Diabetes Institute, said the controversy would raise the bar on requirements for ensuring cardiovascular safety.

“It’s very unlikely we are going to see new drugs for type 2 diabetes now for many years because these sorts of trials can take up to 10 years or longer to evaluate cardiovascular side effects,” he told InSight.

Last week, a US Food and Drug Administration (FDA) joint advisory panel recommended that rosiglitazone (Avandia, GlaxoSmithKline) stay on the shelves with tighter prescribing restrictions.

But the panel’s members were divided over whether the drug should remain on the market. It is now up to the FDA to make a final decision.

Professor Zimmet, who has acted as a consultant for GSK in relation to rosiglitazone, said while the drug was a good one, using pioglitazone (Actos, Eli Lilly) was an alternative.

“In general, people have been wary of the fact that while all of the evidence may not implicate Avandia as has been claimed, until the so-called truth is known, it has been felt that it is safer to use the alternative,” he said.

Professor Zimmet recommended rosiglitazone only be used in younger patients with type 2 diabetes who had no evidence or risk factors for heart disease.

Study raises further concerns
The latest study to raise concerns about the cardiovascular safety of the drug appeared in JAMA on 28 June. (1)

It found that rosiglitazone was associated with an increased risk of stroke, heart failure and all-cause mortality compared with pioglitazone.

The author of an editorial accompanying the paper said the concerns about the drug make it hard to “advance a cogent argument regarding why, exactly, a patient might want to receive the drug or why a physician would choose to prescribe it when there is an available and quite possibly safer alternative”. (2)

Rosiglitazone stays on PBS
The Therapeutic Goods Administration (TGA) said rosiglitazone would remain available on the Pharmaceutical Benefits Scheme but special authority was required for prescribing.

The Product Information (PI) includes a boxed warning against use in patients with ischaemic heart disease and carries warnings that the drug has been associated with an increased risk of angina and heart attack.

“Given the warnings in the PI it is unlikely that many doctors would be prescribing rosiglitazone to new patients; it is most likely to be used in patients already stabilised on the drug, with ongoing monitoring for any cardiac signals,” a TGA spokeswoman said.

In February, the US Senate Committee on Finance criticised the corporate conduct and ethics of GSK on the basis that they allegedly did not provide timely information on the risks associated with the drug’s use. (3) GSK has rejected the criticisms. (4)

According to GSK, 15 000 Australians are taking rosiglitazone. Global sales of the drug totalled $1.2 billion last year, down from $3.2 billion in 2006.

GSK medical director Dr Camilla Chong told InSight if “all the noise was taken away” rosiglitazone remained a safe and effective treatment choice for diabetes.

The final FDA decision is expected in about two months, she said.

1. Graham DJ, Quellet-Hellstrom R, MaCurdy TE, et al. Risk of acute myocardial infarction, stroke, heart failure, and death in elderly Medicare patients treated with rosiglitazone or pioglitazone. JAMA 2010; 304: doi:10.1001/jama.2010.920.

2. Juutlink DN. Rosiglitazone and the case for safety over certainty.

3. Harris G. Caustic government report deals blow to diabetes drug. New York Times 2010; 9 Jul. (accessed Jul 2010).

4. GlaxosmithKline. GSK rejects conclusions of US Senate Committee on Finance Staff Report on Avandia® (rosiglitazone maleate) [press release]. 22 Feb 2010.  (accessed July 2010).

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