Mount Sinai Researchers Discover That Diabetes Drug May Reverse Heart Failure
Study finds drug could have new applications in non-diabetics
Researchers at the Icahn School of Medicine at Mount Sinai have demonstrated that the recently developed antidiabetic drug empagliflozin can treat and reverse the progression of heart failure in non-diabetic animal models. Their study also shows that this drug can make the heart produce more energy and function more efficiently. The results were published in the April 23 issue of the Journal of American College of Cardiology.
“This drug could be a promising treatment for heart failure in both non-diabetic and diabetic patients,” said lead author Juan Badimon, MD, Professor of Cardiology and Director of the Atherothrombosis Research Unit at the Cardiovascular Institute at the Icahn School of Medicine at Mount Sinai. “Our research can lead to a potential application in humans, save lives, and improve quality of life.”
Empagliflozin was approved by the U.S. Food and Drug Administration in 2014. It limits renal sugar resorption and is the first drug in the history of type 2 diabetes proven to prolong survival. While diabetes patients are typically at higher risk of heart failure, past studies have suggested that those who take empagliflozin don’t commonly develop heart failure. Those observations led a team of researchers to question if the drug contains a mechanism, independent of anti-diabetic activity that is linked to heart failure prevention, and whether it could have the same impact on non-diabetics.
Investigators from the Atherothrombosis Research Unit tested the hypothesis by inducing heart failure in 14 non-diabetic pigs. For two months, they treated half of the animals with empagliflozin and the other group with a placebo. The team evaluated the pigs with cardiac magnetic resonance, 3D-echocardiography, and invasive catheterization at three different points in the study (before inducing, one day after inducing, and at the two-month mark). At two months, all animals in the group treated with empagliflozin experienced improved heart function. Specifically, those pigs had less water accumulation in the lungs (less pulmonary congestion, which is responsible for causing shortness of breath) and lower levels of biomarkers of heart failure. Importantly, the left ventricles had stronger contractions (enhanced systolic function), got smaller (less dilated), and were less thick (less hypertrophy), and the heart was a normal shape (less architectural remodeling).
The researchers also found that the drug addressed heart failure by improving cardiac metabolism. The hearts of pigs on the medication were consuming more fatty acids and ketone bodies (three related compounds—acetone, acetoacetic acid, and beta-hydroxybutyric acid—produced during the metabolism of fats) and less glucose, as contrasted with heart failure patients (diabetic and non-diabetic), whose hearts consume more glucose and almost no fatty acids and produces less energy. This boost in metabolism helped the hearts produce more energy and function more strongly and efficiently.
“This study confirmed our hypothesis that empagliflozin is an incredibly effective treatment for heart failure and not only an antidiabetic drug. Moreover, this study demonstrated that empagliflozin is useful for heart failure independently of a patient’s diabetic status. Importantly, empagliflozin switches cardiac metabolism toward fatty acid and ketone body consumption, thus allowing the production of more energy in the heart,” explained co-lead author Carlos Santos-Gallego, MD, postdoctoral fellow at the Icahn School of Medicine at Mount Sinai. “Empagliflozin may be a potentially effective treatment for heart failure patients. This is extremely important because heart failure is a disease with a mortality above 50 percent at 5 years. This study offers a new therapeutic strategy in heart failure, something badly needed given that there have not been new effective drugs for heart failure since the 1990s.”
The authors are currently studying whether empagliflozin is an effective heart failure treatment in non-diabetic human patients in the EMPATROPISM clinical trial.
About the Mount Sinai Health System
Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with 48,000 employees working across eight hospitals, more than 400 outpatient practices, more than 600 research and clinical labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time—discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it.
Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients’ medical and emotional needs at the center of all treatment. The Health System includes approximately 9,000 primary and specialty care physicians and 11 free-standing joint-venture centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida. Hospitals within the System are consistently ranked by Newsweek’s® “The World’s Best Smart Hospitals, Best in State Hospitals, World Best Hospitals and Best Specialty Hospitals” and by U.S. News & World Report's® “Best Hospitals” and “Best Children’s Hospitals.” The Mount Sinai Hospital is on the U.S. News & World Report® “Best Hospitals” Honor Roll for 2024-2025.
For more information, visit https://www.mountsinai.org or find Mount Sinai on Facebook, Twitter and YouTube.