PRESERVATION OF MUSCLE MASS DURING PHARMACOLOGICAL TREATMENT OF OBESITY: THE IMPACT OF INCRETIN-BASED THERAPIES ON BODY COMPOSITION AND THE RISK OF SARCOPENIA

Abstract

Obesity is a chronic disease associated with excessive adiposity and metabolic, functional, and inflammatory alterations that may progressively impair body composition. The introduction of incretin-based pharmacological therapies, particularly glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual GLP-1/GIP receptor agonists, has substantially changed obesity treatment by producing marked weight reductions. However, part of weight loss may occur at the expense of lean mass, raising concerns regarding muscle preservation and the potential risk of sarcopenia, especially among older or clinically vulnerable individuals. This study aimed to analyze body composition changes associated with pharmacological obesity treatment using incretin-based therapies, emphasizing muscle preservation and factors that may influence this process. An integrative literature review was conducted, including publications from 2020 to 2026, using biomedical and scientific databases and descriptors related to obesity, GLP-1 receptor agonists, tirzepatide, semaglutide, lean mass, muscle mass, body composition, and sarcopenia. Current evidence demonstrates that semaglutide and tirzepatide promote substantial reductions in body fat accompanied by reductions in lean mass. However, lean mass should not be interpreted as synonymous with skeletal muscle because it also includes water, organs, and other non-adipose tissues. Recent evidence also indicates that resistance training and adequate protein intake may attenuate lean tissue loss during weight reduction. Therefore, pharmacological obesity treatment should move beyond a weight-centered approach and incorporate periodic assessment of body composition, muscle strength, protein intake, and physical activity, particularly in individuals at increased risk of sarcopenia.