Concerns regarding clinically significant muscle loss during GLP-1–based obesity treatment may be less pronounced than previously feared, according to new findings presented at the European Congress on Obesity 2026. A real-world cohort analysis suggested that most weight reduction achieved with glucagon-like peptide-1 receptor agonist (GLP-1 RA) and glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist (GIP/GLP-1 RA) therapy reflected fat mass loss, while relative skeletal muscle mass remained largely preserved.
The retrospective study included 486 adults with obesity treated with liraglutide, semaglutide, or tirzepatide at a specialized obesity outpatient clinic in Vienna between 2022 and 2025. The cohort had a mean body mass index (BMI) of 37.68 kg/m² and a mean age of 49.9 years; 82% of participants were female. Treatment distribution included semaglutide in 82% of participants, liraglutide in 8%, and tirzepatide in 8%. All participants also received recommendations regarding physical exercise according to current obesity management guidelines.
The analysis evaluated changes in skeletal muscle mass and fat mass during GLP-1 RA or GIP/GLP-1 RA therapy using bioelectrical impedance analysis (BIA), a non-invasive method used to estimate body composition, including fat mass, lean muscle mass, and body water. Changes in body composition were assessed across treatment durations of less than 6 months, 6-24 months, and more than 24 months. Statistical modeling adjusted for repeated measurements, fat mass, treatment duration, age, sex, and baseline BMI.
After a mean treatment duration of approximately 14 months, mean weight loss reached 9.9%. Approximately 80–85% of total weight reduction reflected fat mass loss. Fat mass decreased by 9.0 kg, representing around 18% reduction, whereas skeletal muscle mass decreased by 1.2 kg, or around 5%. Relative skeletal muscle mass was preserved or increased in more than 70% of patients.
Adjusted linear mixed-effects modeling showed that time since treatment initiation was not independently associated with skeletal muscle mass after accounting for fat mass and other variables. Fat mass remained strongly associated with absolute skeletal muscle mass, suggesting proportional body composition changes rather than disproportionate muscle loss during treatment.
The authors stated: “In this real-world cohort, GLP-1RA or GIP/GLP-1 RA therapy was associated with substantial fat mass reduction while largely preserving skeletal muscle mass in relative terms.” They added that the findings “support the concept that GLP-1RA-induced weight loss reflects favourable body composition changes rather than clinically relevant muscle wasting.”
The authors noted several limitations, including the retrospective study design, missing data, lack of a placebo group, and predominance of female participants. They also emphasized that the findings apply to this specific treatment population and duration, and that larger prospective studies are needed to evaluate long-term effects on body composition and muscle preservation.
