GlaxoSmithKline's fallen diabetes drug Avandia has taken another hit after research in the British Medical Journal added further weight to evidence that the drug could put patients at an increased risk from heart disease.
Sales of GSK's franchise - comprised of Avandia (rosiglitazone), Avandamet (rosiglitazone/metformin) and Avaglim (rosiglitazone/glimepride) - were suspended in Europe last September and its use across the Atlantic was severely restricted amid claims the drug is associated with fluid retention and increased risk of heart failure, and the company is facing a string of liability cases as a result.
Since its introduction in 2000 regulators have kept a close eye on the drug's cardiovascular safety profile, but as new data from clinical trials, observational studies and meta-analyses emerged over the last three years, suggesting a possibly increased risk of ischaemic heart disease, Europe's Committee for Medicinal Products for Human Use decided that the benefits no longer outweigh the risks.
Now new research seems to confirm that rosiglitazone is indeed linked with significantly higher odds of serious heart conditions when pitted against Takeda's Actos (pioglitazone), another diabetes therapy in the thiazolidinedione class of drugs.
Researchers from the US and Europe looked at studies involving more than 810,000 patients, and found, that compared with Actos, Avandia was associated with a significant hike in the risk of heart attack (16%), congestive heart failure (23%), and mortality (14%).
This, the authors note, could lead to 170 excess heart attacks, 649 excess cases of heart failure, and 431 excess deaths for every 100,000 patients given Avandia instead of Actos, which, given that around 3.8 million scripts for the former are dished out every year in the US, could have a "considerable" effect on public health.
GSK stands behind Avandia
However, a spokesperson for GSK told PharmaTimes World News that many of the 16 observational studies included in this meta-analysis have already been looked at by the FDA, which actually "strongly recommended against 'combining' dissimilar observational studies into one estimate, as was done in this meta-analysis".
In addition, the spokesperson stressed that, while some observational studies have suggested a higher risk for cardiovascular events with Avandia versus Actos, others have not, and as there are no head-to-head clinical studies with cardiovascular outcomes results between the two drugs definitive conclusions about differences in cardiovascular data are hard to make.
GSK said it stands behind the safety and efficacy of Avandia when used appropriately. "Since 2007, results from six randomized clinical trials with data related to the cardiovascular safety of Avandia have been reported. Taken together, these trials showed that Avandia does not increase the overall risk of heart attack, stroke or death", it points out.