Losing Weight, Losing Muscle? Muscle Health During GLP-1-Based Obesity Therapy

Authors

  • Michael Tsoukas, MD

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and related nutrient-stimulated hormone (NuSH) therapies have transformed obesity pharmacotherapy, delivering weight loss approaching that seen with bariatric surgery. However, concerns have emerged regarding loss of fat‑free mass, skeletal muscle mass, and possible sarcopenia. Reductions in lean mass occur during treatment with semaglutide and tirzepatide, but these changes are generally proportional to total weight loss and occur alongside greater reductions in fat mass, visceral adiposity, and ectopic lipid deposition. The clinical interpretation of lean mass loss is further complicated by limitations of dual-energy X-ray absorptiometry, which cannot distinguish contractile muscle from body water, organs, and connective tissue. Importantly, available data suggest that muscle quality and metabolic function may improve despite reductions in absolute lean mass. Overall, current evidence does not support disproportionate skeletal muscle loss during GLP-1-based obesity therapy. This review summarizes current evidence on GLP-1RA and NuSH-associated changes in muscle mass, discusses mechanisms, identifies populations at risk, and outlines practical strategies to preserve muscle health during treatment.

Author Biography

Michael Tsoukas, MD

Dr. Michael Tsoukas is an Associate Professor of Medicine, Division of Endocrinology of the McGill University Health Centre and Research Investigator of the Research Institute of McGill and Hygea Medical Clinic. He completed his residency in medicine at Tuft’s University in Boston and subsequently trained in Endocrinology at McGill University. Upon completion, he pursued a post-graduate research fellowship in diabetes and obesity at Harvard University, with a focus on GLP-1 receptor pharmacotherapy, brain signaling, and enterohormone treatments. Further training involved pathophysiological regulation of GLP-1 receptor agonists important in energy homeostasis, diabetes, and obesity. Currently, Dr. Tsoukas is the Co-Director of the Metabolic Centre of Excellence of the McGill University Health Centre and Director of Endocrinology at the Montreal General Hospital. He continues to conduct clinical interventional studies and has authored over 50 articles in peer‑reviewed journals, chapters, and abstracts.

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Published

2026-08-26

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Losing Weight, Losing Muscle? Muscle Health During GLP-1-Based Obesity Therapy. (2026). Canadian Diabetes & Endocrinology Today, 4(2), 5–12. https://doi.org/10.58931/cdet.2026.4254

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Volume 4, Issue 2, Summer 2026

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How to Cite

Losing Weight, Losing Muscle? Muscle Health During GLP-1-Based Obesity Therapy. (2026). Canadian Diabetes & Endocrinology Today, 4(2), 5–12. https://doi.org/10.58931/cdet.2026.4254