Study: Mixed results on diabetes drug safety

Avandia increases heart attack risk, while Actos lowers heart attack risk, says new study; Glaxo finds fault with report.

By Aaron Smith, staff writer

NEW YORK ( -- Actos and Avandia have entered the spotlight again, as studies published in a leading medical journal pit the two diabetes drugs against each other by comparing their cardiovascular risks.

In short, the studies say that Actos is safer than Avandia.

Avandia, made by GlaxoSmithKline (up $0.03 to $54.04, Charts), increases the risk of heart attack, while the rival drug Actos from Takeda Pharmaceuticals cuts risk of heart attack, stroke and death, according to study results published in the Sept. 11 edition of The Journal of the American Medical Association.

The study found that both of the drugs increase the risk of heart failure, a well-known fact that is already reflected in the product labels, as mandated by the Food and Drug Administration.

Actos, also known as pioglitazone, reduced the risk of death, heart attack or stroke by 18 percent, but increased the risk of heart failure by 41 percent, in a study co-authored by Dr. Steven Nissen, chief cardiologist for the Cleveland Clinic.

According to a separate study that was also published in JAMA, the diabetes drug Avandia, also known as rosiglitazone, increased the risk of heart attack by 42 percent and more than doubled the risk of heart failure, but did not significantly increase the risk of cardiovascular death. Dr. Sonal Singh of the Wake Forest University School of Medicine in Winston-Salem, N.C. co-authored this study.

Both of these studies used the "meta-analysis" method of gleaning data from existing medical records, rather than conducting clinical trials.

The British drugmaker GlaxoSmithKline disagreed with the studies, saying in a statement on its website, that the meta-analysis method of collecting data has "limitations" and the conclusions drawn from the two studies "do not confirm a difference in the safety profile of Avandia (rosiglitazone) and Actos (pioglitazone)."

"The analyses do not yield data robust enough to guide doctors in selecting appropriate diabetes treatments for their patients," said Glaxo, in the press release. "Comparisons between different meta-analyses with different endpoints and patient populations are even more unreliable."

Robert Spanheimer, senior director of the U.S. diabetes division for the Japanese drugmaker Takeda, was pleased with the study's results saying, it "confirms the confidence that we have in Actos that there is no increased risk of total macrovascular events," which includes heart attack, stroke and death.

Glaxo's blockbuster drug Avandia, which totaled $3 billion in 2006 sales, has come under fire since May, when Dr. Nissen published a report in The New England Journal of Medicine linking the drug to increased risk of heart attacks. Glaxo also criticized that report for being a meta-analysis. It culled 42 studies, including those conducted by Glaxo, rather than conduct a clinical trial in its own right.

In July, FDA panelists voted 22-1 in favor of keeping Avandia on the market. This is a non-binding vote used as a guideline for FDA regulators.

Avandia and Actos are both members of the TZD class of drugs, which are used to help diabetics control their blood-sugar levels.

Avandia and Actos already carry the Food and Drug Administration's "black box" warnings for increasing the risk of heart failure. In August, the FDA said that Glaxo and Takeda both agreed to strengthen these warnings to include information for doctors about monitoring patients for signs for heart failure.

Glaxo is one of the leading European drugmakers, along with the French company Sanofi-Aventis (up $0.82 to $42.64, Charts) and the Swiss company Novartis (up $0.39 to $54.25, Charts). Top of page