A widely prescribed diabetes drug that has shown potential for helping weakened hearts failed to reduce deaths or rehospitalizations in a study of patients with advanced heart failure.

There was a trend toward worse outcomes among the heart-failure patients who also had diabetes, but this could have occurred by chance.

The clinical trial of 300 patients, published Tuesday in the Journal of the American Medical Association, was led by the University of Pennsylvania and involved 24 U.S. centers, including Thomas Jefferson University Hospital, Temple University Hospital, and Lancaster Heart and Stroke Foundation.

The diabetes drug, Novo Nordisk Inc.'s liraglutide, is sold as Victoza for diabetes and Saxenda for obesity treatment. It is part of a growing class of diabetes medications - the fifth was approved just last week - known as glucagon-like peptide 1 agonists. They increase secretion of insulin, the hormone that keeps blood sugar levels in check.

As heart failure progresses, cardiac cells stop properly responding to insulin. The theory behind the new study was that liraglutide would improve this response, thereby reducing metabolic stress in the heart. That theory was bolstered by circumstantial evidence as well as a major cardiovascular safety study of liraglutide required by the Food and Drug Administration.

But the new study found that over six months, patients had no better outcomes on liraglutide than on a placebo. Overall, about 38 percent were rehospitalized because their hearts were so weak, and 12 percent died. Indicators of heart failure such as breathlessness, difficulty walking, and a telltale blood protein did not improve in either group.

Almost 60 percent of these heart-failure patients also had diabetes. None had taken liraglutide before enrolling in the study. For the 91 who were put on liraglutide, outcomes including declining kidney function and rehospitalization were slightly worse than with a placebo, although it was not statistically significant, meaning it could be coincidental.

Lead author Kenneth B. Margulies, a heart-failure and transplant cardiologist at Penn, said diabetics with severe heart failure who are doing well on liraglutide should not quit the drug - but he wouldn't put them on it.

"It does raise a safety concern," Margulies said. "They should not stop [liraglutide]. But if I have a heart-failure patient who needs more diabetes medication, I'd pick something else."

The new study was funded by the National Heart, Lung and Blood Institute.

In March, Novo Nordisk announced results - published last week in the New England Journal of Medicine - of an FDA-mandated study of liraglutide's cardiovascular safety involving 9,000 type 2 diabetics. Compared with placebo, adding liraglutide to standard treatment reduced heart attacks, strokes, and deaths over five years.

Last year, a study that analyzed the records of 19,000 diabetics treated by the Henry Ford Health System in Detroit also found an apparent heart benefit for liraglutide. Patients who had used it were less likely to develop heart failure than those on other diabetes medications.

Given these previous findings, the disappointing new results may mean that as heart failure worsens, it not only lessens the organ's ability to pump blood but also changes the way it metabolizes energy, Margulies and his coauthors speculated.

If so, the stage of heart failure may affect whether a class of drugs is helpful or harmful, Margulies said.

David E. Lanfear, head of heart failure and transplant cardiology at Henry Ford Health System and senior author of the study there, said, "Maybe liraglutide has beneficial effects earlier in the [heart failure] disease process."

As for diabetics with weakened hearts, Lanfear said, "I feel it would be overinterpreting the results to say this class of drugs is hazardous and should not be used, but I agree with the authors that some caution and awareness should be exercised."

Although scientists clearly have a way to go to understand the molecular underpinnings of cardiac metabolism, Margulies believes that new diabetes drugs increasingly will be expected to protect organ function as well as control blood sugar.

"We have a wide array of drugs that are effective at lowering blood sugar," he said. "I would say we are getting to the point where it's not enough to lower blood sugar. We also want to protect the organs that diabetes damages."

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