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 loss comprised 26%–40% of weight loss in recent trials. This case series describes three patients (two female, one male; body mass index: 32.9–51.9 kg m −2 ) who prioritized lean soft tissue preservation strategies during treatment with semaglutide or tirzepatide. Patients engaged in intentional exercise or structured physical activity 4–7 days·week −1 , including resistance training 3–5 days·week −1 . Typical protein intakes were 0.7–1.7 g·kg −1 ·day −1 relative to body mass and 1.6–2.3 g·kg −1 ·day −1 relative to fat-free mass. Changes in weight, fat mass, and lean soft tissue 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 lean soft tissue, while two increased lean soft tissue. These findings highlight the potential for some individuals to preserve or even increase lean soft tissue during treatment with semaglutide or tirzepatide alongside supportive lifestyle strategies.
Tinsley et al. (2025) studied this question.