GLP-1 receptor agonists and skeletal muscle: The risk of sarcopenic obesity and the role of resistance training. A narrative review

Abstract

Background. GLP-1 receptor agonists (GLP-1 RAs) and incretin-based co-agonists have transformed the management of obesity and type 2 diabetes, producing weight loss approaching that of bariatric surgery. Attention has shifted from the quantity of weight lost to its quality - the proportion of fat versus skeletal muscle (lean) mass removed. A meaningful fraction of GLP-1 RA-induced loss is lean tissue, raising concern that these agents may unmask or aggravate sarcopenic obesity Aim. To synthesise evidence on GLP-1 RAs’ effect on skeletal muscle and body composition, characterise the risk of sarcopenic obesity, and appraise resistance training, nutritional and pharmacological countermeasures. Material and methods. A review used PubMed and Google Scholar. RCTs, observational studies, reviews, meta-analyses and relevant preclinical research published in English between 2018 and 2026 were analysed. Results. Absolute lean-mass reductions represent ~20-40% of total weight lost. Contemporary imaging suggests these changes are largely adaptive - commensurate with weight loss - rather than pathological. Principal drivers are reduced energy and protein intake from appetite suppression, catabolic drive, inactivity and anabolic resistance, not direct toxicity. Resistance training with adequate protein (~1.2-1.6 g/kg/day) is the best-established preservation strategy, and activin/myostatin blockers (e.g. bimagrumab) reduce lean-mass loss in early trials. A meta-analysis of tirzepatide trials reported improved physical function versus placebo. Conclusions. Skeletal-muscle loss is a real, quantifiable consequence of GLP-1 RA therapy, though heterogeneous and often adaptive. Older adults, patients with type 2 diabetes, peri- and postmenopausal women, and those with low baseline muscle mass are at greatest risk. Structured resistance training with optimised protein should accompany therapy in at-risk patients; muscle-preserving pharmacotherapy is a rapidly evolving frontier.