A Narrative Review on GLP-1 Receptor Agonists for Obesity in Older Women: Maximizing Weight Loss While Preserving Lean Mass

Obesity in women over 65 represents a growing clinical challenge, particularly due to its association with increased risks of cardiovascular disease, osteoarthritis, frailty, sleep-breathing disorders, and sarcopenia. The prevalence of obesity in this demographic is compounded by age-related metabolic changes and declining physical activity. In this context, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), such as semaglutide and tirzepatide, have emerged as promising pharmacological treatments for weight loss, showing substantial efficacy in reducing body weight and improving metabolic health. However, their use in older populations warrants careful consideration due to the potential risk of muscle loss, which may exacerbate sarcopenia and frailty. This review synthesizes current evidence on the efficacy of GLP-1 RAs for weight loss in older women, exploring both the metabolic benefits and potential risks, particularly with regard to muscle mass preservation. We discuss the mechanisms behind muscle loss associated with GLP-1 RAs, focusing on the balance between fat reduction and the preservation of lean body mass. In phase 3 trials, women aged ≥ 65 years achieved sustained weight loss of 10-20%, with consistent cardiometabolic improvements. Furthermore, we propose practical strategies to mitigate sarcopenia, including physical activity interventions, dietary modifications, and combination therapies aimed at maintaining muscle strength while promoting weight loss. By examining clinical trial data, real-world evidence, and physiological mechanisms, this narrative review aims to provide a comprehensive framework for personalized and safe therapeutic decision-making, addressing the unique needs of older women with obesity.