Impact of Semaglutide on fat mass, lean mass and muscle function in patients with obesity: The SEMALEAN study

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).

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.

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.

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.