Lean Mass Loss in Glucagon-Like Peptide-1/GIP Therapy: Clinical Implications for Obesity and Cardiovascular Care

Glucagon-like peptide-1 receptor agonists and glucose-dependent insulinotropic polypeptide coagonists have revolutionized the treatment of type 2 diabetes and obesity. They demonstrate significant cardiovascular benefits, including a reduction in major adverse cardiovascular events and heart failure hospitalizations. However, these medications are associated with substantial lean body mass loss, comprising 15-45% of total weight reduction. This review examines the pathophysiological mechanisms underlying muscle loss with incretin-based therapies, analyzes clinical trial data on body composition changes, explores the bidirectional relationship between sarcopenia and cardiovascular disease, and evaluates emerging pharmacological and lifestyle interventions to preserve muscle mass. Understanding and mitigating muscle loss is critical for optimizing cardiovascular outcomes, particularly in older adults and those with established heart disease, where sarcopenia is associated with increased mortality and functional decline.