New research presented at the American College of Cardiology 2024 Scientific Session and published in the New England Journal of Medicine reveals that semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, improves heart failure symptoms in patients with type 2 diabetes and heart failure with preserved ejection fraction (HFpEF). The study indicates that these benefits may extend beyond weight loss, offering new hope for individuals with this complex condition.
The trial, involving 616 participants with HFpEF, obesity, and type 2 diabetes, compared once-weekly semaglutide injections to a placebo over one year. Participants on semaglutide experienced significant weight loss and notable reductions in heart failure symptoms compared to the placebo group. These improvements encompassed enhanced quality of life, improved daily functioning, and increased walking distance on a 6-minute walking test.
Mechanisms Beyond Weight Loss
While weight loss contributed to the reduction in symptoms, researchers suggest that semaglutide may exert additional beneficial effects. Yu-Ming Ni, MD, a cardiologist and lipidologist at MemorialCare Heart and Vascular Institute at Orange Coast Medical Center, noted that the drug might reduce inflammation, supported by observed changes in biomarkers such as C-reactive protein (CRP) and NT-proBNP levels. The researchers agreed, writing that the findings “suggest that the mechanisms of benefit with semaglutide may extend beyond weight loss.”
Specifically, the study observed large reductions in C-reactive protein (CRP) and NT-proBNP levels among people receiving semaglutide. CRP levels are related to inflammation and can be an indicator of your risk of developing cardiovascular problems. NT-proBNP is a measure of the severity of heart failure and may be elevated in heart failure with preserved ejection fraction (HFpEF).
Impact on Physical Function
Andrew Choi, MD, associate professor of medicine and radiology at the George Washington University School of Medicine and Health Sciences, highlighted the potential for improved physical function, stating that these improvements would allow people to more easily walk to a neighbor’s house or to a nearby grocery store. A lack of mobility and physical activity can contribute to symptoms of heart failure, something that can be worsened by obesity.
Comparison to Previous Trials
Interestingly, the weight reduction observed in this study was 40% lower than that seen in a previous trial involving heart failure patients without diabetes. Researchers attribute this difference to the use of other glucose-lowering drugs, such as insulin or sodium-glucose co-transporter 2 (SGLT2) inhibitors, which may have blunted the weight loss effects of semaglutide.
Clinical Implications
Richard Wright, MD, cardiologist at Providence Saint John’s Health Center in Santa Monica, Calif., who was not involved in the new research, stated, “This is an important trial which reinforces the concept that patients with the syndrome of heart failure can benefit further from administration of a drug that was originally developed to reduce blood sugar, and has now emerged as an important way to reduce cardiovascular and heart failure events.”
The FDA approved Wegovy last month for reducing the risk of serious heart problems in people who are overweight or have obesity.
