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Effect of glucagon-like peptide-1 receptor agonists and co-agonists on body composition: Systematic review and

Paschalis Karakasis1, Dimitrios Patoulias2, Nikolaos Fragakis1

  • 1Second Department of Cardiology, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Metabolism: Clinical and Experimental
|December 24, 2024
PubMed
Abstract

Insights

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) effectively reduce weight and fat mass but can decrease lean mass. Some GLP-1RAs preserve lean mass better, offering a key consideration for body composition management.

Area of Science:

  • Endocrinology and Metabolism
  • Pharmacology
  • Obesity Research

Background:

  • Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are recognized for their efficacy in reducing body weight.
  • The impact of GLP-1RAs and dual GLP-1/GIP receptor agonists (GLP-1/GIP-RAs) on lean body mass requires further clarification.
  • Understanding body composition changes is crucial for managing overweight/obesity and diabetes.

Purpose of the Study:

  • To evaluate the effects of GLP-1RAs and GLP-1/GIP-RAs on total weight, fat mass, and lean mass.
  • To compare the impact of different GLP-1RAs on body composition in adults with diabetes and/or overweight/obesity.
  • To identify specific agents that may mitigate lean mass loss during weight reduction.

Main Methods:

  • Systematic literature search of Medline, Embase, and Cochrane Library up to November 12, 2024.
  • Inclusion of 22 randomized controlled trials with 2258 participants.
  • Random-effects pairwise and network meta-analyses were employed to compare interventions against placebo or active comparators.

Main Results:

  • GLP-1RAs significantly reduced total body weight (MD -3.55 kg), fat mass (MD -2.95 kg), and lean mass (MD -0.86 kg).
  • Lean mass loss constituted approximately 25% of total weight loss, though relative lean mass percentage remained unaffected.
  • Tirzepatide and semaglutide showed potent weight and fat mass reduction but were less effective in preserving lean mass; liraglutide demonstrated better lean mass preservation.

Conclusions:

  • Potent GLP-1 RAs, including tirzepatide and semaglutide, are associated with substantial weight loss but also significant lean mass reduction.
  • The choice of GLP-1 RA may influence the proportion of lean mass lost during treatment.
  • Further research into strategies for preserving lean mass during pharmacotherapy for obesity and diabetes is warranted.
Keywords:
Body compositionBody weightCardio-renal-metabolic healthDiabetesFat free massFat massGLP-1 receptor agonistLean massObesitySarcopenia

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