IMPACT OF SEMAGLUTIDE USE ON LEAN MASS AND SARCOPENIA RISK: AN INTEGRATIVE REVIEW OF CLINICAL EVIDENCE

Abstract

Semaglutide has emerged as an effective pharmacological strategy for the management of obesity and type 2 diabetes mellitus, promoting significant weight loss. However, its effects on lean mass, muscle function, and the risk of sarcopenia remain under debate, particularly in vulnerable populations such as older adults. The aim of this study was to critically analyze the available clinical evidence regarding the impact of semaglutide on lean mass and sarcopenia risk. This narrative review was conducted based on systematic searches in the PubMed/MEDLINE, SciELO, and ScienceDirect databases, including studies published between 2015 and 2025. Randomized clinical trials, observational studies, and retrospective cohorts conducted in humans that assessed the effects of semaglutide on body composition, lean mass, and sarcopenia-related functional outcomes were included. A total of 19 studies were analyzed. Semaglutide was consistently associated with significant weight loss, primarily driven by fat mass reduction. An absolute reduction in lean mass was observed; however, it was proportionally smaller relative to total weight loss, resulting in a favorable redistribution of body composition. Muscle function outcomes were heterogeneous, with functional preservation in non-elderly adults and a higher risk of functional decline in older and clinically vulnerable populations. In conclusion, semaglutide promotes favorable changes in body composition; however, its effects on lean mass and muscle function are highly dependent on patient characteristics. Although no direct causal relationship with sarcopenia has been established, monitoring of muscle mass and function is recommended, particularly in older adults, along with integrated strategies such as resistance training and adequate protein intake to mitigate potential musculoskeletal risks.