Preserving Muscle Mass During Incretin-Induced Weight Loss

Treatment with appetite suppressant drugs, including incretin-based receptor agonists, generally leads to clinically meaningful weight loss and reduced cardiometabolic risk. However, weight loss may include not only loss of adipose tissue but also loss of skeletal muscle mass, which ultimately may impair physical function and metabolic health. Resistance training is an effective strategy to maintain or increase skeletal muscle mass during weight loss, but its effects during treatment with appetite suppressant obesity medications have been studied insufficiently. This study will investigate whether unilateral resistance training during incretin-based receptor agonist treatment can preserve or improve skeletal muscle mass. Additionally, the study will determine whether preservation of muscle is accompanied by the preservation of muscle function and/or molecular adaptations in skeletal muscle, adipose tissue and blood. Participants will be adults with obesity who are about to start treatment with an incretin-based receptor agonist as part of routine clinical care. During the 13-week intervention, participants will perform supervised unilateral resistance training two times per week, training one leg while the other leg serves as an internal control. Data and tissue collection will take place before treatment start and after 13 weeks. Assessments include whole-body magnetic resonance imaging, blood sampling, skeletal muscle and adipose tissue biopsies, physical function tests, questionnaires, and monitoring of physical activity.

Inclusion Criteria: * Adults aged 18-64 years with obesity. * Planned initiation of incretin-based obesity pharmacotherapy as part of routine clinical care. * Able to participate in supervised unilateral resistance training. * Able to complete physical function tests. * Able to attend study visits at the study center. * Able to provide written informed consent in the Swedish language. Exclusion Criteria: * Contraindication to magnetic resonance imaging. * Medical condition preventing resistance training or physical function testing. * Medical condition preventing skeletal muscle or adipose tissue biopsy. * Inability to understand study information in Swedish or provide informed consent.