By Julie Steenhuysen

CHICAGO, Sept 11 (Reuters) - The diabetes drug Actos cuts the risk of heart attack, stroke and death but raises the risk of heart failure, according to one study published on Tuesday, while a second confirmed disputed findings that rival Avandia raises heart risks.

Actos, made by Takeda Pharmaceutical Co Ltd <4502.T>, lowered the risk of heart attack, stroke and overall death by 18 percent, researchers reported in the Journal of the American Medical Association.

But GlaxoSmithKline's <GSK.L><GSK.N> Avandia increased the risk of heart attack by 42 percent and more than doubled the risk of heart failure in patients who took the drug for at least a year, the second study in the same journal found.

Both drugs already carry U.S. Food and Drug Administration "black box" warnings saying they may cause or worsen congestive heart failure, a chronic condition in which the heart fails to pump blood efficiently to the body's organs.

Dr. Michael Lincoff of the Cleveland Clinic in Ohio said the study showed that while the drugs act in a similar way to help control diabetes, they do not have the same side effects.

Lincoff and colleagues analyzed pooled data on Actos from 16,390 patients enrolled in 19 clinical trials.

"What we can say about pioglitazone (Actos) is not only does it not have the detrimental effect that has been seen with rosiglitazone (Avandia), but it actually has a protective effect," Lincoff said in a telephone interview.

SAME CLASS

Both Actos and Avandia are in a class called thiazolidinediones, or glitazones, which help the body use insulin more effectively. They are among several classes of drugs that treat type-2 diabetes, which affects 194 million people worldwide.

Dr. Bob Spanheimer of Takeda Pharmaceuticals said the Cleveland Clinic analysis of Actos confirms the results of its own clinical trials. "It gives physicians and patients confidence that they can use Actos for treating high blood sugar and insulin resistance," he said.

But Alastair Benbow, GlaxoSmithKline's European medical director, strongly objected to any conclusions based on the two studies. "We believe that the totality of the evidence suggests that the two products have a comparable safety profile," Benbow said in a telephone interview.

The Avandia analysis, done by researchers at Wake Forest University, confirmed other findings that Avandia increased the risk of heart failure. But the study did not find Avandia worsened the risk of death.

Dr. Sonal Singh, who led the study, called for an urgent review to evaluate whether Avandia should stay on the market.

An analysis in the New England Journal of Medicine in May showed Avandia boosted the risk of heart attack by 43 percent.

"Our results confirm this (heart attack) risk, add to the heart failure risk and really show that cardiovascular mortality has not been adequately studied," Singh said in a telephone interview.

BLOCKBUSTER DRUG

Singh estimated about 3.5 million people in the United States take Avandia, which is Glaxo's second-best-selling drug, with global sales of $3.24 billion last year.

"For every 30 patients, there will be one additional heart failure due to Avandia," Singh said. "For heart attack, it is like one in 220."

As for Actos, Singh said he does not think it raises the risk of heart attack, but he is not convinced it is an entirely safe drug.

Sen. Charles Grassley, an Iowa Republican who has been pressing for reform at the Food and Drug Administration, said the studies supported the need for a more proactive drug regulation system. "The FDA's relationship with drug makers is too cozy and has cost the agency its credibility and the public's confidence," Grassley said in a statement.

Dr. Daniel Solomon and Dr. Wolfgang Winkelmayer of Brigham and Women's Hospital and Harvard Medical School in Boston agreed, saying in a commentary that the FDA's requirements for new drug approvals should be tougher, especially when other drugs are available to treat a condition.

(Additional reporting by Ben Hirschler in London)

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