BI and Lilly's diabetes drug Jardiance reverses heart failure in animal models

Neon heart
The SGLT2 inhibitor Jardiance is known to reduce the risk of cardiac death in patients with diabetes, and scientists are working to understand the mechanisms behind that benefit. (Connor Wells/Unsplash)

Eli Lilly’s and Boehringer Ingelheim’s Jardiance, approved by the FDA in 2014, is already a blockbuster in the treatment of Type 2 diabetes. But the companies have been aiming to get the drug approved to treat patients with heart failure who don't have diabetes, and they can now point to promising preclinical results in that indication.

Researchers at the Mount Sinai Icahn School of Medicine in New York showed that in a pig model of heart failure, Jardiance (empagliflozin) improved heart function. The study showed that after two months of treatment with the drug, the left ventricles of the animals’ hearts got smaller and thinner, and they had stronger contractions. The research was published in the Journal of the American College of Cardiology.

Jardiance is an SGLT2 inhibitor that has already shown signs of having a positive effect on heart health. Lilly and BI reported dramatic reductions in cardiovascular risks from their EMPA-REG outcomes trial in diabetes patients back in 2015, and they have been conducting heart trials in people without diabetes for the past couple of years.

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The Mount Sinai researchers took 14 pigs with heart failure and gave Jardiance to half of them. They used advanced imaging techniques like cardiac magnetic resonance and 3D-echocardiography to observe what was happening in the animals’ hearts. They reported improved heart function in all of the treated pigs, reductions in pulmonary congestion—water in the lungs that typically causes shortness of breath—and in biomarkers of heart failure, according to a statement.

RELATED: Lilly, Boehringer add two Jardiance heart failure studies to examine effects on exercise

Lilly and BI have long been aware that Jardiance cuts the risk of cardiac death, but it was never quite clear how the drug was exerting such a positive effect on the heart. The Mount Sinai researchers discovered that the drug improves cardiac metabolism. Specifically, when pigs were put on the drug, their hearts consumed more fatty acids and less glucose, which in turn helped them function more efficiently and produce more energy.

“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,” said co-lead author Carlos Santos-Gallego, M.D., a postdoctoral fellow at Mount Sinai, in the statement.

Improving cardiac metabolism is a strategy that many researchers pursuing heart disease are investigating. Last month, for example, scientists at Ohio State University published research showing that a shortage of a reactive fat compound called acyl-CoA causes a toxic accumulation of bad fat and hampers the ability of the heart to pump efficiently.

As for BI and Lilly, they’re piling on studies designed to show Jardiance’s heart benefits in non-diabetic patients. Last year, they boosted their clinical trial menu by adding two phase 3 studies pitting 12 weeks of Jardiance against placebo in heart failure. The studies, which will wrap up this year, will measure how well the drug reduces symptoms and increases exercise capacity.

The authors of the new Mount Sinai research are participating in a trial sponsored by BI and Lilly that’s designed to further investigate the question of whether Jardiance’s effects on heart health are happening independently of its glucose-lowering mechanism.

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