PHILADELPHIA -In an attempt to correct defects in the energy generation that contribute to poor pump function among heart failure patients, researchers examined whether the diabetes drug liraglutide, could improve the condition of patients with advanced heart failure. Despite improvements in blood sugar control, the therapy did not improve the clinical stability or pumping action of the heart in patients with advanced heart failure. A team of researchers led by Kenneth B. Margulies, MD, a professor of Medicine and research director for Heart Failure and Transplantation, and Thomas Cappola, MD, ScM, chief of the division of Cardiovascular Medicine in the Perelman School of Medicine at the University of Pennsylvania, detailed findings from the Functional Impact of GLP-1 for Heart Failure Treatment (FIGHT) study in a paper published today in the Journal of the American Medical Association (JAMA). Data from this study was initially presented at the American Heart Association Scientific Sessions 2015 in November.
Heart failure, a chronic condition in which the heart does not pump enough blood through the body, affects more than 5 million Americans.
"Abnormalities in the way the heart generates energy from fats and glucose, including resistance to the normal actions of insulin, have been shown to contribute to a patient's risk of heart failure. But no current heart failure treatments target these metabolic derangements," said Margulies, the principle investigator of the study. "Because liraglutide counters insulin resistance, and earlier pilot studies suggest that severely weakened hearts have the greatest metabolic defects and potential benefit, it seemed most appropriate test the efficacy of liraglutide in a group of patients with advanced heart failure. Unfortunately, the results were not what we had anticipated."
The FIGHT study, conducted by the U.S. National Heart Lung and Blood Institute's Heart Failure Clinical Research Network, is the first multicenter trial to evaluate the use of glucagon-like peptide-1 receptor agonists - an injectable drug commonly used to treat type-2 diabetes - for the treatment of high-risk heart failure patients with reduced ejection fraction, a measure of the heart's inability to pump blood. Researchers randomized 300 diabetic and non-diabetic participants with high-risk heart failure - those who had been hospitalized for heart failure within the past two weeks - into two groups: those to receive daily liraglutide injections and those receiving daily placebo injections. Subjects were assessed at baseline and eased onto the proper dosage for the first month. During the six-month study period, measurements of heart structure and function with echocardiography, serial assessments of subjects' activity tolerance with six-minute walk tests, and quality of life questionnaires did not reveal any significant favorable or unfavorable effects of liraglutide in these patients.
"The results indicate that while liraglutide acted as intended, controlling blood sugar and promoting weight loss in diabetic participants, there was not a significant impact on heart failure. Interestingly, liraglutide had no effect on blood sugar or weight loss among the non-diabetic patients in the study," Margulies said. "Although this did not support our hypothesis of beneficial effects in patients with advanced heart failure, additional studies are required to explore whether patients with earlier stages of heart failure might benefit from liraglutide or other GLP-1 agonists."
Since one-third of patients with heart failure also have diabetes, and other treatments to lower blood sugar in diabetics have increased the risk of heart failure, Margulies notes that it remains important to establish the safety of any diabetes therapy in patients with heart failure. Additional research, he says, will ultimately determine whether GLP-agonists, like liraglutide, can be used safely among patients with various stages of heart failure.
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The Functional Impact of GLP-1 for Heart Failure Treatment (FIGHT) study was supported by grants from the National Heart, Lung, and Blood Institute (NHLBI) (coordinating center: U10 HL084904; regional clinical centers: U01 HL084861, U10 HL110312, U109 HL110337, U01 HL084889, U01 HL084890, U01 HL084891, U10 HL110342, U10 HL110262, U01 HL084931, U10 HL110297, U10 HL110302, U10 HL110309, U10 HL110336, U10 HL110338).
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Journal
JAMA