A woman with cystic fibrosis treated with semaglutide experienced 14.8% body weight reduction over 12 months while improving blood sugar control, but simultaneously lost muscle mass, muscle strength, and bone mineral density despite receiving tailored exercise and nutrition interventions. This represents the first documented case tracking body composition changes during GLP-1 therapy in cystic fibrosis. The muscle and bone losses occurred even with professional guidance, suggesting these effects may be inherent to the drug mechanism rather than preventable through lifestyle modifications. This finding raises significant concerns about GLP-1 agonists in populations already vulnerable to muscle wasting and bone disease. While semaglutide's metabolic benefits are well-established, this case suggests the weight loss may come at an unacceptable cost for certain patient groups. The parallel loss of both muscle and bone tissue indicates potential interference with anabolic processes beyond simple caloric restriction. For the millions using GLP-1 drugs, this highlights the critical need for comprehensive body composition monitoring, not just weight tracking, and challenges the assumption that targeted interventions can prevent adverse effects in all populations.