Glucagon Like Peptide-1 Receptor Agonists for Sarcopenia and Muscle Wasting Disorders: A Systematic Review of Efficacy and Mechanisms.
Level 5 - mechanism / opinion, no new human data
Systematic review synthesizing primarily preclinical animal models with limited clinical data
PubMed 41400575 · doi:10.14336/AD.2025.1165
What was done
The authors conducted a systematic review synthesizing 20 preclinical and clinical studies to evaluate the efficacy, phenotypic outcomes, and molecular mechanisms of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in sarcopenia and skeletal muscle wasting disorders.
What was found
The abstract reports no numerical values, effect estimates, or statistical significance metrics. In animal studies, GLP-1RAs improved grip strength and skeletal muscle cross-sectional area while maintaining body weight within defined dosage ranges. Reported preclinical mechanisms included upregulation of myogenic factors (MyoD, MyoG), enhanced mitochondrial biogenesis, and suppression of proteolytic markers (MuRF1, MAFbx) and inflammation via AMPK/SIRT1/NF-κB/Myostatin signaling. Conversely, limited clinical studies reported overall body weight loss accompanied by a decline in lean mass.
Why it matters
This review highlights a critical discrepancy between animal models showing anabolic muscle preservation with GLP-1RAs and human studies showing lean mass loss, indicating caution and the need for targeted human trials in sarcopenic populations.
Limits
The abstract provides no quantitative data, effect sizes, or meta-analytic pooling. The body of evidence relies heavily on animal models that may not translate to human pathophysiology. Human studies were limited in number, and specific patient demographics, GLP-1RA compounds, and dosing regimens were not specified in the abstract.
Cited by
- contradicts GLP-1 receptor agonists ramp up AMPK, which can cause muscle wasting in people who do not consume adequate protein.