Resistance Training to Prevent Muscle Loss During Treatment With Tirzepatide

Incretin-based pharmacotherapies induce significant weight loss and represent a paradigm shift in obesity treatment. However, particularly fast weight loss may be accompanied by a significant loss of muscle mass, which is associated with a reduced metabolic rate at rest and during physical activity, increased insulin resistance, limited mobility, and potential long-term adverse effects. The aim of this clinical trial is to examine the effects of resistance training versus standard of care on contractile thigh muscle volume in patients receiving the dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonists 'tirzepatide'.

Inclusion Criteria: Age 1. Are ≥ 18 years and ≤ 60 years of age Weight 2. Have a body mass index (BMI) of ≥ 30 kg/m2 3. Have a history of at least 1 self-reported unsuccessful dietary effort to lose body weight 4. In the investigator's opinion, are well motivated, capable, and willing to * learn how to self-inject the investigational medicinal product (IMP), as required for this protocol * inject the IMP, and * comply with trial procedures for the duration of the trial, including adherence to scheduled visits, the prescribed resistance training program (if assigned to the experimental group), lifestyle recommendations, and other requirements as specified in the protocol Sex and contraceptive/barrier requirements \[only for women\] 5. Women of childbearing potential (WOCBP) may be enrolled only if one of the following applies: * They are completely abstinent as their preferred and usual lifestyle or exclusively in a same-sex relationship as their preferred and usual lifestyle and agree to remain abstinent or stay in a same-sex relationship without sexual relationships with males until 30 days after the last injection (\> 5 half-lives of tirzepatide) * They have a negative serum pregnancy test result at screening followed by a negative urine result ≤ 24 hours prior to the first injection, and they agree to use, from screening until 30 days after the last injection, either: * one highly effective method of contraception (failure rate \5 kg within 3 months prior to screening 4. Have a prior or planned surgical treatment for obesity (excluding liposuction or abdominoplasty if performed \>1 year prior to screening) 5. Have or plan to have endoscopic and/or device-based therapy for obesity or have had device removal within the last 6 months prior to screening (e.g., mucosal ablation, gastric artery embolization, intragastric balloon, duodenal-jejunal endoluminal liner) 6. Have obesity induced by other known endocrinologic disorders (e.g., Cushing syndrome) or diagnosed monogenetic or syndromic forms of obesity (e.g., Melanocortin 4 Receptor deficiency or Prader Willi Syndrome) Note: If endocrinological disorder is suspected, a dexamethasone suppression test should be performed to assess for possible hypercortisolism Other Medical 7. Are currently breastfeeding 8. Have structural cardiovascular disease (e.g., ischemic cardiovascular disease, heart failure, previous cerebrovascular accident \[stroke\]) 9. Have atrial fibrillation 10. Have uncontrolled hypertension (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg) 11. Have any visual, neurological, musculoskeletal, or other physical impairment that, in the opinion of the investigator, would prevent the participant from independently and appropriately self-administering the IMP and/or performing the resistance training program as required by the protocol (e.g., significant muscle or joint pain, significantly limited range of motion) 12. Have renal impairment measured as estimated glomerular filtration rate (eGFR) \