Malnutrition and Sarcopenia as Reasons for Caution with GLP-1 Receptor Agonist Use in HFpEF

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as promising agents to improve outcomes in patients with heart failure with preserved ejection fraction (HFpEF) and obesity. GLP-1 is an incretin hormone produced endogenously by the gut in response to food intake; it augments insulin release and inhibits glucagon secretion, thereby reducing hepatic glucose production. As such, GLP-1RAs were developed for glycemic control in patients with diabetes, with the first approval in 2005. In addition, GLP-1 agonists delay gastric emptying and inhibit appetite, resulting in decreased food intake and weight loss. This led to the approval of the first GLP-1RA for the treatment of obesity in 2014. Given the well-described role of obesity in the pathophysiology of HFpEF, there is a strong biological rationale supporting the potential for GLP-1RAs to improve outcomes in HFpEF. True to form, the STEP-HFpEF (Semaglutide Treatment Effect in People with Obesity and HFpEF) randomized clinical trial demonstrated that semaglutide led to significant weight loss (13% reduction) and improvements in quality of life. 1 Kosiborod MN Abildstrom SZ Borlaug BA Butler J Rasmussen S Davies M et al. Semaglutide in patients with heart failure with preserved ejection fraction and obesity. N Engl J Med. 2023; 389: 1069-1084 Crossref PubMed Scopus (87) Google Scholar