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Study on new diabetes drug sees heart benefit, with caveat

Some advise: Try older pills first

CHICAGO - The widely used diabetes pill Actos appears to lower a patient's chances of death, heart attack, or stroke, unlike its beleaguered chief rival, Avandia, a new analysis shows.

It, however, also carries an increased risk of nonfatal heart failure, the analysis showed, confirming earlier studies. Heart failure is also a side effect with Avandia. Such problems led one diabetes specialist to recommend that both drugs be considered second choices behind older, less expensive pills.

Heart failure "is a significant side effect," said Dr. Alvin Powers, director of Vanderbilt University's diabetes center. "No one would say that you should be on these drugs to prolong your life." He was not involved in the research.

Older drugs, including Metformin, are available in generic form and can cost less than 20 cents a day - 10 times less than Avandia and Actos. The older drugs can stop working, however, and doctors may try newer pills instead of having patients resort to insulin injections.

When the older drugs lose effectiveness, Actos "is a drug that clearly I think is preferable," said Dr. A. Michael Lincoff, who coauthored the Actos study with a Cleveland Clinic colleague, Dr. Steven Nissen.

Their research was paid for with a $25,000 grant from Takeda Global Research & Development, a Deerfield, Ill., division of Actos's maker, Takeda Pharmaceutical Co. of Osaka, Japan. Takeda had no role in designing their analysis.

The review, appearing in today's Journal of the American Medical Association, is the biggest to date on Actos. It pools the results of 19 studies involving some 16,000 people. Compared with patients taking other diabetes drugs or none, Actos patients had an 18 percent reduced risk of death, heart attack, or stroke.

The findings are important because heart attacks are a leading cause of death in people with diabetes, the authors said.

The same researchers wrote an analysis earlier this year linking Avandia with increased heart attack risks, and a drug advisory panel is recommending stronger warnings on that drug's packaging. The FDA has not acted on that recommendation.

The agency is requiring label warnings of the heart failure risks for both Avandia and Actos.

In the new analysis, death, heart attack, or stroke occurred in 375 of 8,554 patients, or 4.4 percent, versus 450, or 5.7 percent, of 7,836 patients on other drugs or no treatment.

A separate analysis of four Avandia studies in the journal found heart attack and heart failure risks similar to earlier reports.

Takeda's Dr. Robert Spanheimer said the Actos analysis adds "scientific validity" to previous data on the company's drug.

GlaxoSmithKline PLC, Avandia's maker, said the new report doesn't prove Actos is safer than Avandia. The company added that the Avandia review amounts to selective analysis of old data.

An editorial in the medical journal said the new information underscores the need for quicker regulatory action when signs of trouble with new drugs surface.

Actos and Avandia each have been used by 7 million patients since their introduction in 1999. They belong to a troubled newer class of diabetes treatments.

Actos and Avandia control blood sugar by improving the body's sensitivity to insulin. Avandia can increase levels of LDL cholesterol, the "bad" kind; while Actos can increase HDL cholesterol, the good kind, and can lower trigylceride levels - effects that may help explain the study results, Nissen said.

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