A network meta-analysis of 43 randomised trials found that GLP-1 receptor agonists significantly reduce body fat, fat mass, visceral and subcutaneous adipose tissue and liver fat in adults with overweight or obesity, with or without type 2 diabetes. However, high doses of liraglutide, semaglutide and tirzepatide also reduced lean mass. No overall change in total lean tissue was seen.
Systematic review — Systematic review and network meta-analysis. Population: Adults with overweight or obesity with or without type 2 diabetes. Sample size: 3379 participants. Interventions: Liraglutide 1.8 mg/day; Semaglutide 1.0 mg weekly; Tirzepatide 15 mg weekly.
Subcutaneous GLP-1 receptor agonists were more effective than control in reducing total body fat, fat mass, visceral adipose tissue area, subcutaneous adipose tissue area and liver fat content from baseline. No significant difference was found for change in total lean tissue. Liraglutide 1.8 mg/day, semaglutide 1.0 mg weekly and tirzepatide 15 mg weekly each significantly decreased lean mass, with standardised mean differences ranging from -1.09 to -0.50. The network included 43 RCTs with 3379 participants and 17 interventions or dosages.
This paper provides comparative effect estimates on fat and lean mass for GLP-1 receptor agonists, including tirzepatide and liraglutide, which is useful when interpreting body-composition outcomes in trials of these agents. It does not establish whether the observed lean-mass loss is clinically meaningful, nor does it address mechanisms or long-term safety.
Peptide profiles: Tirzepatide, Liraglutide.
All indexed evidence: Tirzepatide trials & papers, Liraglutide trials & papers.
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