Preserving Muscle Mass During Incretin-Induced Weight Loss

Treatment with incretin-based obesity medications leads to clinically meaningful weight loss and reduced cardiometabolic risk. However, the weight lost includes not only adipose tissue but also skeletal muscle, which 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 incretin-based obesity medications have not been studied. This study will investigate whether unilateral resistance training during incretin-based receptor agonist treatment can preserve or improve skeletal muscle volume. The study will also examine whether training affects muscle strength and fatigue tolerance, body composition, cardiac structure and function, and molecular profiles in skeletal muscle, adipose tissue and blood. Participants will be women 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 twice weekly, training one leg while the other leg serves as an internal control. Assessments before treatment start and after 13 weeks include whole-body and cardiac magnetic resonance imaging, blood sampling, skeletal muscle and adipose tissue biopsies, knee-extensor strength and fatigue tests, and questionnaires. An additional intermediate sampling of blood and tissue (week 4-6) will be collected only in participants who consent to an extra visit.

Inclusion Criteria: * Women aged 18-64 years with obesity, BMI ≥35 kg/m² * 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. * A weight reduction \>5% during the last 3 months. * Patients diagnosed with any known serious chronic illness, including type 1 or 2 diabetes (or a randomly measured fasting plasma glucose \>7 mmol/L). * Angina pectoris, coronary heart disease or congestive heart failure (NYHA Class III- IV). * Severe renal impairment (creatinine clearance (GFR) \2 hours per week. * Inability to understand the study information in Swedish or provide informed consent.