Real-world effectiveness of oral semaglutide on body weight, composition, and metabolic parameters in patients with obesity without diabetes.

INTRODUCTION: Obesity is a chronic adiposity-based disease with limited long-term response to lifestyle interventions. Oral semaglutide, currently approved for type 2 diabetes, may represent a therapeutic option for obesity, although real-world evidence is scarce. OBJECTIVE: To evaluate, in a real-world clinical setting, changes in body weight, body composition, and muscle strength after treatment with oral semaglutide in patients with obesity. Secondary objectives were to assess changes in metabolic and inflammatory parameters and depressive symptoms. METHODS: We conducted a multicenter, prospective, observational study including 70 adults with obesity without diabetes who initiated oral semaglutide as part of routine clinical care. RESULTS: After 4 months, mean body weight decreased by 5.4kg, mainly due to a reduction in fat mass, accompanied by decreases in waist circumference, and visceral fat. Lean mass showed a small reduction, while muscle strength remained unchanged. Clinically meaningful weight loss was achieved by 44.3% of patients. Improvements were also observed in metabolic parameters, inflammatory markers, and depressive symptoms. CONCLUSIONS: In real-world clinical practice, treatment with oral semaglutide at doses approved for type 2 diabetes was associated with short-term weight loss in patients with obesity, primarily driven by fat mass reduction, with preservation of muscle strength. These findings should be interpreted considering the observational design and lack of a comparator group.