Preservation of Lean Soft Tissue During Weight Loss Induced by GLP-1 and GLP-1/GIP Receptor Agonists: A Case Series

GLP-1 receptor agonists (e.g., semaglutide) and dual GLP-1/GIP receptor agonists (e.g., tirzepatide) are effective for reducing body weight and fat mass, though lean soft tissue (LST) loss comprised 26–40% of weight loss in recent trials. This case series describes three patients (2 female, 1 male; BMI: 32.9–51.9 kg/m2) who prioritized LST preservation strategies during treatment with semaglutide or tirzepatide. Patients engaged in intentional exercise or structured physical activity 4–7 d·wk-1, including resistance training 3–5 d·wk-1. Relative protein intakes were 0.8–1.7 g·kg-1·d-1. Changes in weight, fat mass, and LST were: -33.0%, -53.4%, and -6.9% (Case 1); -26.8%, -61.6%, and +2.5% (Case 2); and -13.2%, -46.9%, and +5.8% (Case 3). Accordingly, one patient lost 8.7% of weight as LST, while two increased LST. These findings highlight the potential for some individuals to preserve or even increase LST during treatment with semaglutide or tirzepatide alongside supportive lifestyle strategies.