Just as GlaxoSmithKline’s diabetes drug Avandia (rosiglitazone) is preparing Monday to face a US Food and Drug Administration advisory panel on concerns over possible links to cardiovascular adverse events, new research coming out of the UK suggests that Avandia and Eli Lilly/Takeda’s Actos (pioglitazone) double the risk of heart failure, with fluid retention caused by the drugs providing the trigger.

The findings are based on a meta-analysis of more than 78,000 patients, which estimates that one in every 50 patients taking the drugs over a 26-month period will require hospital admission due to heart failure. “This means that the diabetes drugs could have caused thousands of additional cases of heart failure, creating a substantial burden on hard-pressed health services,” said Dr Yoon Loke, a clinical pharmacologist at UEA’s School of Medicine, Health Policy and Practice. The results are published in the August edition of the journal Diabetes Care.

In the UK, prescriptions for the drugs, known as thiazolidinediones, have doubled over the last three years and they were taken by more than 1.5 million people in England alone last year.

The new research was undertaken by Loke, working with colleagues at Wake Forest University in the US. In the UK, Avandia and Actos are recommended for use on the country’s National Health Service, but Loke now says: “I think NICE [the UK's cost-effectiveness body, the National Institute for Health and Clinical Excellence] should re-evaluate their decision to recommend these diabetes drugs.”

The researchers also looked in detail at more than 200 cases of patients with heart failure related to the diabetes drugs and found that the problem developed even in patients taking low doses of the drugs. Furthermore, around 25% of cases occurred in people under the age of 60, even without a history of cardiovascular disease. “Most patients in the studies did not have heart failure prior to starting on treatment with these drugs,” said Dr Loke. “There doesn’t seem to be a group of patients who are safe from these side effects.”

“These drugs are taken by more than seven million diabetic patients in the US alone, suggesting that several thousand could be harmed,” said co-author Dr Sonal Singh of Wake Forest University.

GSK statement

“The risk of heart failure in diabetes patients and with use of these medicines is well recognised and is clearly identified in prescribing information to doctors in the UK,” said Alastair Benbow, European Medical Director, GlaxoSmithKline.

The analysis does not include the results from either the ADOPT or RECORD studies study, two recently published long-term prospective studies in which the risk of heart failure is assessed in patients taking rosiglitazone. In ADOPT the same number of congestive heart failure serious adverse events were reported for rosiglitazone versus metformin in a drug naive diabetic population. Meanwhile, in the RECORD interim analysis, rosiglitazone was associated with significantly more cases of CHF when compared with patients on control – metformin and sulphonylurea. Despite the increase in CHF however, the primary outcome of cardiovascular hospitalizations and death showed no significant difference between the rosiglitazone group and the metformin/sulphonylurea group.

GSK finished: "It is important for physicians to use rosiglitazone in appropriate patients in line with the European Summary of Product Characteristics, which states that rosiglitazone should not be used in patients with CHF. GSK is confident in the overall safety profile of rosiglitazone when used appropriately."