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

Abstract

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.

Keywords: GIP (glucose-dependent insulinotropic polypeptide); GLP-1 receptor agonists; exercise; fat-free mass; lifestyle modification; muscle mass; nutrient-stimulated hormone-based therapy; protein.

FIGURE 1

Illustration of an integrated approach consisting of pharmacotherapy, a protein-rich diet (PRO), and resistance training to optimize body composition among users of new generation anti-obesity medications (AOMs). The bar graph represents the theoretical relative contribution of fat mass (solid bars) and lean mass (striped bars) to weight loss under 4 conditions: AOM alone (pink), AOM plus PRO (AOM + PRO; dark blue), AOM plus resistance training (AOM + RT; light blue), and the combination of all 3 (AOM + PRO + RT; yellow). The relative contribution of lean body mass to total weight loss with AOMs is suggested to range between 20% and 50% [11]. The data for AOM alone (pink) are inferred from body composition changes measured using dual-energy x-ray absorptiometry in a double-blind trial of once-weekly semaglutide in adults with overweight or obesity [8]. Simulated data for AOM + PRO are based on meta-analyses demonstrating that increased protein intake improves body composition by decreasing fat mass while preserving lean mass during weight loss [35,36]. AOM + RT data are simulated from studies showing that combining liraglutide with exercise reduced body fat percentage twice as much as medication alone while preserving lean mass [69], as well as evidence supporting the role of resistance training in increasing lean body mass in adults with overweight or obesity [71]. Finally, the combined approach (AOM + PRO + RT) is simulated from original research [90] and systematic reviews [88], showing that the combination of high-protein diets and exercise training leads to the greatest reductions in body fat and lean loss of lean mass during weight loss.