Sculpting Success: The Importance of Diet and Physical Activity to Support Skeletal Muscle Health during Weight Loss with New Generation Anti-Obesity Medications

Obesity is a public health crisis, with prevalence rates tripling over the past 60 y. Although lifestyle modifications, such as diet and physical activity, remain the first-line treatments, recent anti-obesity medications (AOMs) have been shown to achieve greater reductions in body weight and fat mass. However, AOMs also reduce fat-free mass, including skeletal muscle, which has been demonstrated to account for 20% to 50% of total weight loss. This can equate to ∼6 kg or 10% of total lean mass after 12–18 mo, a loss comparable to a decade of human aging. Despite questions surrounding the clinical relevance of weight loss-induced muscle loss, the importance of adopting lifestyle behaviors such as eating a protein-rich diet and incorporating regular resistance training to support skeletal muscle health, long-term weight loss maintenance, and overall well-being among AOM users should be encouraged. Herein, we provide a rationale for the clinical significance of minimizing weight-loss-induced lean mass loss and emphasize the integration of diet and physical activity into AOM clinical care. Owing to a lack of published findings on diet and physical activity supporting skeletal muscle health with AOMs, specifically, we lean on findings from large-scale clinical weight loss and diet and exercise trials to draw evidence-based recommendations for strategies to protect skeletal muscle. We conclude by identifying gaps in the literature and emphasizing the need for future experimental research to optimize skeletal muscle and whole-body health through a balance of pharmacotherapy and healthy habits.