Semaglutide 2.4 mg Demonstrates Large Reductions in Heart Failure Related Symptoms and Physical Limitations in People with Obesity-Related Heart Failure with Preserved Ejection Fraction and Type 2 Diabetes

KANSAS CITY, MO – Saint Luke’s Mid America Heart Institute today announced results from the STEP HFpEF DM trial showing that compared with placebo, once-weekly semaglutide 2.4 mg produced greater reductions in heart failure-related symptoms and physical limitations,  improved exercise function, and led to greater weight loss in adults with heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes.

The findings, presented today at the American College of Cardiology Scientific Session in Atlanta, Georgia and published simultaneously in the New England Journal of Medicine, show large improvements in patient-reported Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS), measuring the symptoms and physical limitations due to heart failure.

Obesity and type 2 diabetes are common in patients with heart failure with preserved ejection fraction and characterized by a high burden of symptoms and functional impairment. There are currently no approved therapies that specifically target obesity-related heart failure with preserved ejection fraction in people with type 2 diabetes.

“Obesity forms a ‘common soil’ that can lead to the development of heart failure with preserved ejection fraction and type 2 diabetes, and patients living with both conditions suffer from an especially high symptom burden but have few available treatment options,” said Dr. Mikhail Kosiborod, lead study investigator and cardiologist at Saint Luke’s Mid America Heart Institute, Kansas City, USA. “Today’s results, especially when combined with those from the STEP-HFpEF trial, open a new chapter of targeting obesity as a new and effective treatment strategy in patients with obesity-related HFpEF, both with and without diabetes.”

The mean change in the KCCQ-CSS was a 13.7-point increase at 52 weeks with semaglutide 2.4 mg vs 6.4 points with placebo, leading to an estimated treatment difference of 7.3 points (p<0.001). Mean change in body weight was a 9.8% reduction with semaglutide 2.4 mg vs. 3.4% reduction with placebo, leading to an estimated treatment difference of 6.4% weight reduction (p<0.001).

STEP HFpEF DM also demonstrated a mean increase in 6-Minute Walking Distance (6MWD) of 12.7 meters at 52 weeks with semaglutide vs. a mean decrease of 1.6 meters with placebo leading to an estimated treatment difference of 14.3 meters (p=0.008). Semaglutide also reduced inflammation, as measured by the levels of high-sensitivity C-reactive protein (hsCRP).

The safety profile of semaglutide 2.4 mg was consistent with previous studies; fewer serious adverse events were observed with semaglutide 2.4 mg compared with placebo.

About heart failure with preserved ejection fraction (HFpEF), obesity and type 2 diabetes
There are 64 million people living with heart failure worldwide. HFpEF is now the most common form of heart failure, comprising approximately 50% of all cases. Importantly, 80% of people with HFpEF also live with overweight or obesity and nearly half have type 2 diabetes.

About STEP HFpEF Program
The primary objective of STEP HFpEF Diabetes trial was to investigate the effects of semaglutide 2.4 mg  subcutaneous once-weekly on symptoms, physical function, and body weight compared with placebo in patients with obesity-related HFpEF and Type 2 Diabetes. STEP HFpEF included 616 people with symptomatic HFpEF (ejection fraction ≥45%) and obesity (BMI ≥30 kg/m2). Dual primary endpoints were change in KCCQ-CSS from baseline to week 52 and change in body weight from baseline to week 52; with key secondary endpoints of change in 6MWD from baseline to week 52, hierarchical composite endpoint (all cause death, heart failure events, difference in KCCQ-CSS change and difference in 6MWD change from baseline to week 52), and change in C-reactive protein from baseline (screening) to week 52.

The previously published STEP HFpEF trial – another study of 529 participants with obesity-related HFpEF but without type 2 diabetes – also demonstrated larger reductions in heart failure-related symptoms and physical limitations, greater improvement in exercise function, and greater degree of weight loss with semaglutide versus placebo.

About Saint Luke’s Mid America Heart Institute
Saint Luke’s Mid America Heart Institute, a part of Saint Luke’s Health System and a teaching affiliate of the University of Missouri-Kansas City School of Medicine, is one of the distinguished cardiovascular programs in the country. Its legacy of innovation began more than 40 years ago when it opened as the nation’s first freestanding heart hospital. Since then, the Heart Institute has earned a global reputation for excellence in the treatment of heart disease, including interventional cardiology, cardiovascular surgery, imaging, heart failure, transplant, heart disease prevention, cardiometabolic disease, women’s heart disease, electrophysiology, outcomes research, and health economics. Saint Luke’s Mid America Heart Institute cardiologists offer personalized cardio-oncology care, where our experts diagnose and treat heart conditions in patients who have been or are being treated for cancer.

With more than 100 full-time, board-certified cardiovascular specialists on staff, Saint Luke’s Mid America Heart Institute offers one of the country's largest heart failure and heart transplant programs, has the largest experience with transcatheter aortic valve replacement in the Midwest, and is a global teaching site for the newest approaches in coronary revascularization. The Heart Institute's cardiovascular research program encompasses clinical areas as well as centers of excellence and core laboratories. It continues to serve as one of the four Analytic Centers, along with Duke, Harvard, and Yale, for the American College of Cardiology's National Cardiovascular Data Registry.

Saint Luke’s Mid America Heart Institute is ranked 47th in the nation for Cardiology, Heart & Vascular Surgery by U.S. News & World Report and is the third hospital in the U.S. to achieve Comprehensive Cardiac Center certification from The Joint Commission.

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