There is serious concern about top-selling diabetes drug rosiglitazone (Avandia), its safety, as well as the whole system by which medications are regulated, evaluated and promoted worldwide, according to a BMJ (British Medical Journal) investigation. Dr. Fiona Godlee, BMJ Editor-in-Chief, thinks Avandia should not have been licensed; she believes it should be withdrawn.

There should be better access to raw data used to license drugs, as well as more robust regulatory processes, to allow examination by the scientific community, Godlee added.

The investigative article reveals that the Commission on Human Medicines advised the Medicines and Healthcare products Regulatory Agency (MHRA), the UK’s regulatory body for drugs, to withdraw the drug because “risks of rosiglitazone outweigh its benefits..it no longer has a place on the UK market”.

Update June 7th, 2013 – an FDA advisory panel voted to loosen the restrictions on Avandia (rosiglitazone), which have been in force since 2010.

Doctors in the UK are currently advising that new patients should not be started on rosiglitazone, and those already on the medication should be reviewed so that alternative therapies may be considered. Patients at higher risk of heart disease are being advised to stop taking the medication.

The FDA (Food and Drug Administration, USA) approved rosiglitazone in 1999, while the EMA (European Medicines Agency) did the same in 2000, to help lower blood sugar in type 2 diabetes patients.

Since those two approvals, a number of studies have linked rosiglitazone to a small overall increase in heart attack risk. However, in July 2010 the Scientific Advisory Committee, which advises the FDA, said that it was safe enough to remain on the market. The Committee’s recommendations are not binding, but the FDA usually goes along with what it says.

Dr. Deborah Cohen, investigations editor of the BMJ, obtained data under the Freedom of Information Act that note “a paucity of evidence during the European approval process and outline concerns from some panel members about the long term risks and benefits of rosiglitazone.”

Several experts have since commented on the poor evidence base, as well as very little long-term information on the drug’s cardiovascular safety.

The reports also comments on the quality of data used by GlaxoSmithKline, the makers of Avandia (rosiglitazone), to demonstrate that the drug did not lead to increased heart problems compared to other diabetes medications. Concern is also expressed regarding the lack of publicly available trial results for independent scientific scrutiny, a lack of transparency in the European system, and the ability of the European regulator to assess individual patient data.

The report highlights pressures on regulatory agencies by diabetes specialist doctors to approve rosiglitazone, and agency failure to act swiftly on emerging safety information.
,br> Two experts comment on today’s report.

Professor Nick Freemantle, University of Birmingham, believes an overhaul in the standards of regulatory trials to minimize the chances of a similar situation occurring in other clinical areas in the future is needed:

In order to learn from our mistakes, we must improve the quality of safety data from clinical trials on all new health care interventions, not just antidiabetic drugs.

Professor John S.Yudkin, University College London, says that doctors should concentrate more on what matters to patients:

Ten years after the release of rosiglitazone, we still cannot accurately quantify the harm to which we were exposing our patients.

Prof. Freemantle accepts that some blame must lie with clinicians for not insisting on better proof of long-term benefit. He adds:

We need to be absolutely certain that our long term treatments for type 2 diabetes are not causing the very harm they are meant to prevent. And if the regulatory bodies do not insist on clear evidence of greater benefit than harm, they are failing in their basic purpose.

Scientists at the Duke Clinical Research Institute (DCRI) wrote in the American Heart Journal (June 2013 issue) that Avandia is not associated with a higher heart attack risk than metformin/sulfonylurea. The DCRI team re-assessed the original findings of RECORD.

Written by Christian Nordqvist