SAGE Open Medical Case Reports (SCO)Preservation of Lean Soft Tissue During Weight Loss Induced by GLP-1 and GLP-1/GIP Receptor Agonists: A Case Series

⚠️ Small Study / Early Comparative Evidence

This case series described three adults with obesity who received semaglutide or tirzepatide while emphasizing structured physical activity, resistance training, and dietary protein. Body weight decreased by 13.2% to 33.0%, while DXA measurements showed a 6.9% lean soft tissue reduction in one patient and increases of 2.5% and 5.8% in two patients. The observations contrast with lean soft tissue losses reported in GLP-1–based obesity trials, but the uncontrolled design cannot establish whether exercise, protein intake, medication exposure, or other factors explain the outcomes.

Clinical Considerations

• All three patients completed structured activity four to seven days weekly, including resistance training three to five days weekly.
• Reported protein intake ranged from 1.6 to 2.3 g/kg/day relative to fat-free mass, though dietary data were self-reported.
• Weight declined 33.0%, 26.8%, and 13.2%, with substantially greater reductions in fat mass than lean soft tissue.
• One patient lost 8.7% of total weight as lean soft tissue, while the other two gained lean soft tissue during treatment.
• DXA measures lean soft tissue rather than skeletal muscle directly, limiting conclusions about muscle mass, strength, or physical function.
• Three selected cases without controls cannot establish causality or generalizability; randomized trials are needed to evaluate targeted exercise and nutrition strategies.

Practice Applications

• Recognize body composition as a relevant consideration during substantial pharmacotherapy-associated weight loss, rather than relying exclusively on scale weight.
• Discuss physical activity, resistance exercise, and nutrition within individualized obesity care, while avoiding prescriptive conclusions from three cases.
• Interpret DXA lean soft tissue changes separately from direct measures of skeletal muscle mass, strength, and functional performance.
• Monitor future controlled trials assessing whether structured resistance training or defined protein targets preserve lean tissue during incretin therapy.
• Avoid presenting these observations as evidence that specific exercise or protein regimens will prevent lean tissue loss.