Muscle Mass Preservation as a Therapeutic Challenge in GLP-1 Receptor Agonist Therapy

Abstract

Weight loss induced by GLP-1 receptor agonists is accompanied by a substantial reduction in lean body mass, typically accounting for 25–40% of total weight loss. Although this proportion is consistent with physiological weight reduction, preservation of skeletal muscle remains essential due to its key role in metabolic health, insulin sensitivity, physical function, and long-term weight maintenance. Excessive muscle loss may increase the risk of sarcopenia, reduced strength, and adverse metabolic adaptations. Current evidence indicates that lean mass loss during GLP-1 therapy is primarily driven by energy deficit, reduced protein intake, and adaptive physiological responses rather than direct drug-induced catabolism. Nevertheless, GLP-1 receptor agonists may improve muscle quality through reductions in intramuscular fat and improved insulin sensitivity. Preservation of muscle mass therefore requires a multimodal strategy combining pharmacotherapy with resistance exercise and adequate protein intake. Among these interventions, resistance training appears to be the most effective approach for minimizing lean mass loss and maintaining functional capacity during treatment.