Abstract
Aims
Semaglutide, a GLP-1 receptor agonist, has shown efficacy in promoting weight loss. However, limited data exist on its impact on lean mass, muscle function, and metabolic adaptations. The SEMALEAN study aims to evaluate these parameters in patients with obesity treated with Semaglutide (2.4 mg).
INTRODUCTION
Obesity has become a significant public health challenge due to its rising prevalence and associated comorbidities including: type 2 diabetes, cardiovascular disease, obstructive sleep apnea, osteoarthritis, cancers (breast, colorectal…). In addition to lifestyle interventions and bariatric surgery, pharmacological treatments have emerged to improve weight management outcomes. Among these, glucagon-like peptide-1 (GLP-1) receptor agonists have shown substantial efficacy in inducing weight loss. GLP-1 is an incretin hormone released from enteroendocrine cells in the gut in response to food intake. Initially developed to manage hyperglycemia in type 2 diabetes, GLP-1 receptor agonists, such as Semaglutide, are now recognised for their potent effects on appetite regulation, gastric emptying, and food intake. Semaglutide, administered once weekly at a dose of 2.4 mg, has demonstrated significant weight loss outcomes in clinical trials, with reductions in body weight exceeding 15% in many patients. These outcomes highlight its potential as a therapeutic option for obesity, particularly in cases where lifestyle interventions alone are insufficient.
Despite the efficacy of GLP-1 receptor agonists in reducing body weight, limited data exist on their impact on body composition, including changes in fat mass, lean mass, muscle function, and the potential development of sarcopenia defined by a loss of muscle mass and function. Current data suggest a preservation of muscle mass and function during Semaglutide treatment. However, these data are highly heterogeneous. Few studies have used DXA, the gold standard for measuring body composition, and even fewer have assessed muscle function. Data are very limited for the highest dose of Semaglutide (2.4 mg), as most studies have focused on the 1 mg dose.
Preserving muscle mass during weight loss is critical, as sarcopenia is associated with an increased risk of morbidity and mortality, particularly in patients with obesity. Muscle mass is also a key determinant of energy expenditure. Low energy expenditure and impaired fat oxidation are risk factors for weight gain, but also cause resistance to weight loss. Thus, assessing the effects of Semaglutide on lean mass and muscle function is critical to fully evaluating the benefits and risks of such treatments, and to focus more on the quality of weight loss and its maintenance rather than the absolute weight loss.
The SEMALEAN study aims to investigate the effects of Semaglutide on body composition, focusing on lean mass and muscle function over 1 year of treatment.
Materials and Methods
This prospective study enrolled 115 patients with obesity between February 2022 and November 2024. Body weight, body composition (measured by DXA), muscle function (handgrip strength), and resting energy expenditure (REE) were assessed at baseline (M0), 7 months (M7), and 12 months (M12). Subgroup analyses examined the impact of sex, type 2 diabetes, previous GLP-1 use, and history of bariatric surgery...
Results
A total of 106 patients (68.9% female; mean BMI 46.3 kg/m2) completed the study. Weight loss was significant, with mean reductions of 10% at M7 and 13% at M12; 59% of patients achieved ≥10% weight loss. Total fat mass decreased by 14% at M7 and 18% at M12, while lean mass initially declined (−3 kg at M7) but stabilised thereafter. Handgrip strength improved significantly (+4.5 kg at M12), and the prevalence of sarcopenic obesity decreased from 49% at baseline to 33% at M12. REE normalised to lean mass increased significantly from M7 to M12. Subgroup analyses revealed greater weight and fat mass loss in women, while patients with type 2 diabetes or prior GLP-1 analogue use showed attenuated responses. Patients with a history of bariatric surgery exhibited the most pronounced reductions in body composition parameters.
Conclusions
The SEMALEAN study highlights the significant impact of Semaglutide 2.4 mg on weight loss, fat mass reduction, and muscle function improvement, with preserved lean mass and metabolic efficiency. These findings underscore the importance of a comprehensive approach to obesity management, addressing not only weight loss but also functional and metabolic adaptation.