GLP-1 receptor agonists, body composition, skeletal muscle and risk of sarcopaenia: from promising findings in animal models to debated concern in human studies

Jun 26, 2025Diabetes & metabolism

GLP-1 receptor drugs, body fat and muscle, and risk of muscle loss: from hopeful animal results to uncertain effects in people

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Abstract

Favourable effects on skeletal muscle mass (SMM) and mitochondrial health were observed in rodent models treated with GLP-1-based therapies.

GLP-1-based therapies may induce clinically relevant weight loss in people with type 2 diabetes and clinical obesity.
Some human studies reported excessive loss of fat-free mass (FFM) and SMM, while others suggested a protective effect against sarcopaenia.
Mixed results in human studies could stem from misinterpretation of SMM measurements and inadequate investigation of muscle function and structure.
Maximizing fat loss while preserving lean tissue mass and function is a key goal in obesity treatment.
Further research is needed to accurately assess the effects of GLP-1 therapies on muscle structure, function, and performance, particularly in at-risk populations.

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BACKGROUND: - Glucagon-like peptide-1 (GLP-1)-based therapies induce a clinically relevant weight loss, which is associated with overall better prognosis in people with type 2 diabetes and/or clinical obesity. However, a risk of excessive reduction in fat-free mass (FFM) and skeletal muscle mass (SSM), potentially leading to sarcopaenia in at-risk patients, is currently a matter of debate as this negative effect could minimize their benefit/risk balance.

METHODS: - An extensive literature search to detect animal and human studies that investigated the effects of GLP-1-based therapies on changes in body composition (FFM and SMM), muscle strength, structure, and function.

RESULTS: - Favourable effects on SMM, intramuscular lipid deposition, inflammation and mitochondrial health were consistently reported in different rodent models with GLP-based therapies. However, mixed results were reported in human studies, some reported an excessive FFM/SMM loss while others arguing for a protective effect against sarcopaenia (including less myosteatosis). This controversy may result from misinterpretation of SMM derived from FFM changes and a lack of studies that properly investigate SMM, muscle function and structure in humans.

CONCLUSION: - Maximizing fat loss while preserving lean (muscle) tissue mass and function is a central goal of modern obesity pharmacological treatments. Currently, available data preclude to have a definite conclusion about positive/negative effects of GLP-1-based therapies on muscle. Further investigations using accurate methodologies to assess not only SMM but also muscle structure, function (strength) and performance are needed to better analyse the effects of GLP-1-based therapies, especially among individuals at higher risk of sarcopaenia, older patients and frail people.

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GLP-1 receptor agonists, body composition, skeletal muscle and risk of sarcopaenia: from promising findings in animal models to debated concern in human studies

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