Older patients treated with diabetes drug Avandia, sold by GlaxoSmithKline PLC and Actos, made by Takeda Pharmaceutical Co. Ltd, have a significant increased risk of heart attack, congestive heart failure compared to the other diabetes drugs, a new study, made by an independent nonprofit group that evaluates treatments in Toronto, showed.

According to the International Diabetes Federation, an estimated 246 million people, almost 6 percent of the world’s adult population, suffer from diabetes and 3.8 million a year die from it.

Both Avandia and Actos belong to a class of drugs called thiazolidinediones or TZDs, introduced in the late ‘90s as an adjunctive treatment for type-2 diabetes.

“Our study suggests that at least in this high-risk population, the harms of the drug may outweigh the benefits, even in patients without obvious baseline cardiovascular disease," suggested the study’s lead author, Dr. Lorraine L. Lipscombe of the Institute for Clinical Evaluative Sciences in Toronto.

The study analyzed drug use and health outcomes for 159,000 people registered in Ontario, aged 65 and older and treated for type-2 diabetes for a median of 3.8 years, through March 2006. Of those patients, 2,268 were on treatment with Avandia.

Dr. Lorraine and her colleagues found a 60 percent increased risk of congestive heart failure, a 40 percent higher risk of heart attack and a 29 percent higher risk of overall death among the patients who were treated with Avandia. They did not see a higher risk for any of these for Actos and that is because the study might have had too few Actos patients, about half the number on Avandia.

The U.S. labels for both Avandia and Actos have carried a “black box” warning against their use in patients with advanced congestive heart failure since August. However, the new study revealed that Avandia raised the risk of heart failure even in patients with no history of the condition.

The Food and Drug Administration released a statement on Tuesday referring to the new findings of the study.

“This new study we have just seen today does not change FDA’s recommendations. The information FDA provided for the most recent labeling change remains accurate — the data are inconclusive and we have added a boxed warning to the labeling to ensure that health care professionals and patients are aware of this potential risk and can take this into account as they make individual prescribing decisions,” the statement said.

Steven Nissen, the Cleveland Clinic’s chief of cardiovascular surgery reported himself in The New England Journal of Medicine in May the results of a study carried on by him, which found that Avandia patients were 43 percent more likely to have a heart attack or be hospitalized for blocked coronary arteries than others. The study created controversy at the time, Glaxo saying that Dr. Nissen overstated the drug’s risk.

According to Nissen, Lipscombe’s study “has a lot of appeal. It’s independent, it’s not funded by industry and it’s huge. It’s real data,” he said.

On the other hand, Glaxo said the study had “significant limitations and generates misleading conclusion.”

Avandia was the world’s best selling diabetes drug and London-based Glaxo’s second-biggest drug in 2006, gaining the company $3.3 billion that year. The sales have fallen by more than half in the U.S. since the heart risks were first reported. Most patients switched to Actos, which has diminished risk, according to market research firm IMS Health Inc. and Citigroup Inc. analysts. This has led to 11 percent decline for Glaxo’s shares.

The findings of the study were published in Tuesday issue of The Journal of the American Medical Association.