Treating Sarcopenic Obesity in the Era of Incretin Therapies: Perspectives and Challenges

Sarcopenic obesity, a subtype of obesity, is marked by reduced skeletal muscle mass and function, or sarcopenia, and poses a significant health challenge to older adults as it affects an estimated 28.3% of people aged >60 years. This subtype is unique to older adults as aging exacerbates sarcopenia and obesity due to changes in energy metabolism, hormones and inflammatory markers, and lifestyle factors. Traditional treatments for sarcopenic obesity have been focused on exercise and dietary modifications to reduce fat while maintaining muscle mass. Newer glucagon-like peptide 1 receptor agonists (GLP-1RA) and dual gastric inhibitory polypeptide/GLP-1 receptor agonists (GIP/GLP-1RAs), including liraglutide, semaglutide, and tirzepatide, have shown great promise to reduce weight, treat obesity-related complications, improve physical function, and improve quality of life, in younger clinical trial populations. However, the use of GLP-1RAs and GIP/GLP-1RAs has not been exhaustively evaluated in older adults with sarcopenic obesity. These medications come with the risk of loss of muscle mass and an increased rate of adverse events. Thus, clinicians should use them cautiously by weighing the potential benefits against their risks. Herein, we discuss a possible approach to using GLP-1RAs and GIP/GLP-1RAs in patients with sarcopenic obesity, including considerations for patient identification, monitoring, maintenance, and discontinuation. In this article we also discuss the emerging treatments that will be available, which may include activin type II receptor antibodies and selective androgen receptor agonists. We conclude by highlighting the advancement of geroscience as a promising field for individualizing treatments in the future. Article Highlights Sarcopenic obesity, reduced muscle mass and strength coupled with obesity, poses significant health risks to older adults. Aging exacerbates sarcopenia and obesity due to metabolic, hormonal, inflammatory, and lifestyle changes. Traditional interventions emphasize exercise and diet to reduce fat mass while preserving muscle mass. Incretin therapies show promise in weight reduction and physical improvement in younger populations but are minimally studied in older adults. These medications can be used to treat several obesity-related complications, which older adults with sarcopenic obesity are prone to developing. These medications need to be used cautiously among older adults, considering potential muscle mass loss and adverse events.