Glucagon-like Peptide-1 Receptor Agonists, Tirzepatide and Muscle-Related Body Composition: A Systematic Review and Meta-Analysis

Background/Objectives: GLP-1 receptor agonists (GLP-1RAs) and the dual GIP/GLP-1 receptor agonist tirzepatide reduce body weight, but their effects on muscle-related body-composition measures and physical function remain uncertain. We evaluated changes in skeletal muscle mass (SMM), lean mass, and related outcomes and performed a focused meta-analysis of compatible bioelectrical impedance analysis (BIA) cohorts. Methods: PubMed, Embase, and the Cochrane Library were searched for studies published from 2009 through 30 April 2026. Eighteen unique studies reported in 19 publications were included. A post hoc quantitative synthesis pooled five BIA-derived cohorts from four studies in adults with type 2 diabetes using a random-effects model. Results: Nineteen publications describing 18 unique studies (total n = 3541; age range 45.4–76.7 years) were included. The pooled within-group change across compatible BIA cohorts was −0.90 kg (95% CI −1.21 to −0.59; I2 = 57.3%). This estimate does not establish a causal drug effect. DXA and BIA outcomes were synthesized separately because they are not interchangeable. Conclusions: GLP-1RA treatment was accompanied by a small within-group reduction in heterogeneous BIA-derived muscle-mass estimates, but the certainty of this evidence was very low. DXA-derived lean mass, BIA-derived muscle mass, and sarcopenia are not interchangeable outcomes. The available data do not establish a drug-specific loss of contractile muscle or functional decline. Standardized controlled studies incorporating muscle strength and physical performance are required.