Could a Diabetes Drug Reverse Heart Failure?

A new study found that the Eli Lilly and Boehringer Ingelheim (BI) drug empagliflozin (Jardiance), used to treat diabetes, could also treat and even reverse heart failure. The findings of the trial were published in the April issue of the Journal of the American College of Cardiology.

“Empagliflozin cardiac benefits in the EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) trial cannot be explained exclusively by its antihyperglycemic activity,” the researchers wrote in their abstract. “The hypothesis was that empagliflozin’s cardiac benefits are mediated by switching myocardial fuel metabolism away from glucose toward ketone bodies (KB), which improves myocardial energy production.”

Empagliflozin ameliorates adverse ventricular remodeling in non-diabetic heart failure by enhancing myocardial energetics. https://t.co/phvoeqYNRr #JACC pic.twitter.com/W19YJ0yBxL

— JACC Journals (@JACCJournals) April 22, 2019

The research team induced heart failure in 14 nondiabetic pigs by 2-h balloon occlusion of the proximal left anterior descending artery. For two months, the animals received either empagliflozin or placebo. Cardiac MRI and 3D echocardiography were used to evaluate the animals, and simultaneous blood sampling of the coronary artery and coronary sinus was used to evaluate myocardial metabolite consumption. Myocardial samples were used for molecular evaluation. The animals were compared to nonmyocardial infarction animals.

Empagliflozin ⤵️ adverse cardiac remodeling and HF in a nondiabetic porcine model. Empagliflozin improving myocardial energetics, enhancing LV systolic function, and ameliorating adverse LV remodeling VÍA @JACCJournals 📎https://t.co/d5jCjxsC0B @redGDPS @secardiologia pic.twitter.com/xwtqfnaLkP

— Alfonso Valle (@ValleAlfonso) April 15, 2019

Empagliflozin Superior to Placebo: Results Could ‘Save Lives’

The empagliflozin group had improved cardiovascular outcomes compared to the placebo group: after two months, the treatment group had lower left ventricular (LV) mass, reduced LV dilatation, and less LV sphericity compared to the placebo group, as well as improved LV systolic function and neurohormonal activation.

“Compared with nonmyocardial infarction, control animals increased myocardial glucose consumption mainly through anaerobic glycolysis while reducing utilization of free fatty acid (FFA) and branched-chain amino acid (BCAA),” the study authors wrote. “Empagliflozin-treated pigs did not consume glucose (reduction in myocardial glucose uptake, and glucose-related enzymes) but instead switched toward utilization of KB, FFA, and BCAA (increased myocardial uptake of these 3 metabolites, and enhanced expression/activity of the enzymes implicated in the metabolism of KB/FFA/BCAA).”

EMPA-REG: Empagliflozin, CV outcomes and mortality in Type 2 Diabetes ca. 2015 from @NEJM#VisualAbstract by @kidney_boy#ISNWCN 🇦🇺🦘 #Nephpearls
👉🏼 https://t.co/6NSu71ck43 pic.twitter.com/JY25epdnfs

— Edgar V. Lerma 🇵🇭 (@edgarvlermamd) April 14, 2019

Juan Badimon, MD, lead study author, said the results could hold promise for diabetic and nondiabetic patients.

“Our research can lead to a potential application in humans, save lives, and improve quality of life,” Dr. Badimon, professor of cardiology and director of the Atherothrombosis Research Unit at the Cardiovascular Institute at the Icahn School of Medicine at Mount Sinai, said in a press release.

“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,” added 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 five 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.”

A nice manuscript showing benefits of empagliflozin beyond T2D. If also shown with the EMPEROR RCTs results, empa will be a very good CV drug that also lowers blood glucose… https://t.co/JGPu3medwf

— Xavier Garcia-Moll (@xgmoll) April 16, 2019