Glucagon Like Peptide-1 Receptor Agonists for Sarcopenia and Muscle Wasting Disorders: A Systematic Review of Efficacy and Mechanisms.

Muscle wasting disorders, including sarcopenia and skeletal muscle atrophy, are increasingly prevalent among older adults and those with metabolic comorbidities. Sarcopenia, a progressive age-associated condition, involves the decline in skeletal muscle mass, strength, and physical performance, affecting millions of people globally. These disorders significantly elevate the risks of frailty, falls, and premature mortality, contributing to a growing burden on healthcare systems. Current interventions, including resistance exercise and dietary supplementation, have shown limited effectiveness, particularly among individuals with concurrent conditions such as type 2 diabetes (T2D). Notably, glucagon-like peptide-1 receptor agonists (GLP-1RAs), initially developed for glycemic and weight control, have demonstrated promising effects in preclinical models of muscle degeneration. In this review, we analyzed 20 preclinical and clinical studies on sarcopenia and muscle wasting disorders. Animal studies yielded promising results, including increased grip strength and enhanced skeletal muscle cross-sectional area (CSA), while body weight remained stable within a defined dosage range. Mechanistically, GLP-1RAs mitigate muscle wasting by upregulating myogenic factors (MyoD, MyoG), promoting mitochondrial biogenesis, and suppressing proteolysis (MuRF1, MAFbx) and inflammation via AMPK/SIRT1/NF-κB/Myostatin signaling. In contrast, limited clinical studies showed body weight reduction accompanied by a decline in lean mass following GLP-1RA treatment. Collectively, these results highlight the low dose-dependent anabolic potential of GLP-1RAs on skeletal muscle, while clinical evidence indicates simultaneous weight and lean mass loss. These findings suggest low-dose GLP-1RAs as potential therapy for sarcopenic obesity or early sarcopenia with metabolic comorbidities, warranting comprehensive clinical trials that incorporate multimodal strategies to preserve muscle mass during treatment.