FDA panel to probe safety of Avandia

Diabetic patients who consume GlaxoSmithKline’ Avandia to keep their sugar levels at bay may now have to shift to some substitute drug as the most commonly used diabetes drugs Avandia may in fact double the risk of heart failure, according to a new study conducted by researchers at Wake Forest University School of Medicine.

The findings, based on a review of research studies and case reports involving more than 78,000 patients, published online in May 2007 by Diabetes Care and will appear in the August print issue.

In their study, the researchers concluded that the risk of heart failure increased up to 100 percent higher in patients who took thiazolinediones (which combines Avandia and Actos) to treat type 2 diabetes.

The researchers estimate that for every 50 patients taking the medications over a period of 26 months, one person will develop heart failure and need admission to hospital.

The drugs, approved by the National Institute for Health and Clinical Excellence for use on the NHS to treat Type 2 diabetes, are not recommended for people suffering from, or at risk of, heart failure. But the new study links an increased risk even to those who have never suffered heart failure.

After the release of new study that linked Avandia to a 43% increased risk of heart attacks, the US health agency Food and Drug Administration reviewed dozens of drug studies and presented their report on Thursday.

In the report, the American health watchdog stated that the widely used diabetes drug Avandia increases the chance of serious heart problems, including a 30% to 40% higher risk of myocardial ischemia, or decreased flow of blood to the heart.

Actos, a drug manufactured by Takeda Pharmaceutical Co., carried no similar risks, according to the FDA documents that released in advance of an FDA advisory panel meeting on Monday.

Approved by the FDA on May 28, 1999, Rosiglitazone maleate, marketed as Avandia, is a drug that reduces glucose (sugar) level in the blood by increasing the level of insulin. It belongs to the antibiotic drug class called "thiazolidinediones” and is used to treat type II diabetes. Actos (pioglitazone) is another member from this class.

Avandia’s drug class "thiazolidinediones” affects a gene called PPAR-gamma and helps the body to use insulin more effectively. GlaxoSmithKline, the manufacturer of Avandia medicines cautioned from the beginning that the drugs were not suitable for patients at risk of, or with a history of, heart failure.

It even warned that patients who combined the drugs with insulin treatments were at increased risk for this complication. But the latest analysis found that the drug equally affected those with no risk for heart failure, even in the absence of insulin.

In wake of concerns about the diabetes drugs’ risks, two advisory panels for the FDA are re-examining both drugs. FDA's division of drug risk evaluation is due to hold a meeting on Monday to review the drug's safety.

In the meeting, the FDA panel could recommend stronger, "black box" warnings or withdraw the drug from the market. If recommended by FDA advisory committee, the expanded warnings, which will appear in a black-ruled box displayed prominently on the prescribing information, would note that patients with heart disease or who are taking insulin should not use the drug.

Although FDA is not bound to follow its advisory panel's recommendations, it generally follows their guidance. The health agency makes a decision on whether a product should be approved after evaluating all data and considering the recommendations of the advisory committee.

GlaxoSmithKline is the second largest pharmaceutical company after Pfizer with its headquarters in UK. It has received a perfect score of 100 percent from the Human Rights Campaign Foundation’s in 2005.

GSK also entered into a controversy in December 2006 when a committee of obstetricians published their opinion in the journal Obstetrics & Gynecology regarding the increased risk of birth defects due to intake of the antidepressant Paxil by pregnant women.