Comparative Effects of Individual Glucagon-Like Peptide-1 Receptor Agonist-Based Medications on Direct Measurement of Body Composition Among Adults With Overweight or Obesity With or Without Type 2 Diabetes: A Systematic Review and Network Meta-Analysis of Randomised Controlled Trials.
Level 1 - systematic review of randomized trials
Systematic review and network meta-analysis of randomized controlled trials
PubMed 42209204 · doi:10.1111/dom.70884
What was done
A systematic review and frequentist random-effects network meta-analysis evaluated 43 randomized controlled trials (3,379 participants) comparing individual GLP-1 receptor agonists (17 interventions/dosages) against controls in adults with overweight or obesity, with or without type 2 diabetes. Searches included six databases and grey literature up to November 3, 2025. Evaluated direct body composition outcomes included total body fat (%), fat mass (kg), visceral adipose tissue (VAT) area, subcutaneous adipose tissue (SAT) area, liver fat content (%), total lean tissue (%), and lean mass (kg).
What was found
Subcutaneous GLP-1RAs were more efficacious than controls at reducing total body fat, fat mass, VAT, SAT, and liver fat from baseline (exact effect sizes not provided in the abstract). No significant differences were observed for change in total lean tissue percentage. However, subcutaneous liraglutide 1.8 mg/day, semaglutide 1.0 mg/week, and tirzepatide 15 mg/week significantly decreased absolute lean mass from baseline, with standardized mean differences ranging from -1.09 to -0.50.
Why it matters
This review clarifies that while GLP-1RA medications consistently reduce both overall and ectopic adipose tissue, higher doses drive statistically significant losses in absolute lean body mass.
Limits
The abstract omits numeric effect sizes and confidence intervals for fat depot reductions. Clinical and functional consequences of lean mass loss (such as muscle strength or physical performance) were not detailed in the abstract.
Cited by
- contradicts A study showed that the bulk of lean mass loss observed during GLP-1 receptor agonist therapy comes from the eradication of liver fat rather than muscle loss.