Body Composition Remodelling During GLP-1-Based Therapy: A Systematic Review and Meta-Analysis Using a Hierarchical...

Body composition changes during glucagon-like peptide-1 (GLP-1)-based therapy remain incompletely characterized, particularly regarding their effects on adiposity, muscle quantity, and muscle quality. We conducted a systematic review and meta-analysis using a predefined physiological framework to evaluate body composition remodelling during GLP-1-based therapy.

We searched PubMed, Embase, and Cochrane CENTRAL from inception through May 2026 for studies evaluating GLP-1 receptor agonists or dual incretin therapies reporting longitudinal body composition outcomes in adults. Outcomes were classified into adiposity, muscle quantity, muscle quality, and body weight domains. Primary analyses prioritized comparative evidence and included one physiologically coherent outcome per study and domain. Random-effects meta-analyses were performed using restricted maximum likelihood estimation with Hartung-Knapp adjustment.

Nineteen studies met the eligibility criteria, including comparative and exploratory single-arm investigations. Three comparative studies contributed to the primary adiposity meta-analysis and two to the primary muscle quantity meta-analysis. Comparative analyses suggested a direction toward greater reductions in adiposity during GLP-1-based therapy. However, only three studies contributed to this analysis, and the pooled estimate was characterized by substantial between-study heterogeneity and a wide confidence interval crossing the null. Evidence regarding muscle quantity was based on two comparative studies and remained highly heterogeneous and imprecise. Muscle quality outcomes could not be quantitatively synthesized because of methodological heterogeneity and incomplete variance reporting and were therefore evaluated narratively. Exploratory single-arm analyses showed reductions in adiposity and body weight, whereas changes in muscle quantity varied across studies.

Current comparative evidence suggests a possible direction toward greater reductions in adiposity during GLP-1-based therapy. However, the limited number of comparative studies, substantial between-study heterogeneity, wide confidence intervals, and low to very low certainty of evidence preclude definitive conclusions regarding preferential fat loss or preservation of skeletal muscle health. Reductions in lean mass should not be interpreted as synonymous with sarcopenia, but the available evidence is also insufficient to exclude clinically relevant muscle loss in susceptible populations. These findings should therefore be considered hypothesis-generating and require confirmation in adequately powered comparative studies incorporating standardized assessments of muscle quantity, muscle quality, strength, and physical performance.

CRD420261411693.