Resistance Training to Prevent Muscle Loss During Treatment With 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 \<1% per year) or * two complementary forms of effective contraception Note: The summary of product characteristics (SmPC) indicates that concomitant use with tirzepatide may reduce systemic exposure to oral contraceptives, particularly during dose escalation, potentially decreasing their contraceptive effectiveness. Therefore, the use of a barrier method in combination with oral contraceptives is required. Informed Consent 6. Are sufficiently proficient in German to understand the trial procedures and informed consent information 7. Are capable of providing written informed consent Exclusion Criteria: Medical Conditions Diabetes Related 1. Have known Type 1 Diabetes, a history of Type 2 Diabetes (including those in remission), a history of ketoacidosis of any aetiology, or a history of hyperosmolar hyperglycaemic state or coma 2. Have at least one laboratory value suggestive of diabetes during screening including: * glycated hemoglobin A1c (HbA1c) ≥6.5% (≥48 mmol/mol) * fasting glucose ≥126 mg/dL (≥7.0 mmol/L) Note: If a blood sample is collected under non-fasting conditions and the random glucose value is ≥200 mg/dL (≥11.1 mmol/L), an additional fasting blood sample will be obtained to confirm or exclude diabetes. Obesity Related 3. Have a self-reported reduction in body weight \>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) \<30 mL/min/1.73 m2, calculated by Chronic Kidney Disease Epidemiology (CKD-EPI) 2021 creatinine-based equation during screening 13. Have a known clinically significant gastric emptying abnormality (e.g., severe gastroparesis or gastric outlet obstruction) or chronically take drugs that directly affect gastrointestinal motility 14. Have a history of chronic or acute pancreatitis Note: If acute pancreatitis is suspected, laboratory assessment of pancreatic amylase and/or lipase 15. Have thyroid-stimulating hormone (TSH) outside the range of 0.4 to 6.0 mIU/L at the screening visit Note: Participants receiving treatment for hypothyroidism may be included, provided their thyroid hormone replacement dose has been stable for at least 3 months and their TSH at screening falls within the range indicated above. Note: Participants with a history of subclinical hypothyroidism but a TSH at screening within the range indicated above may be included if, in the investigator's opinion, the participant is unlikely to require initiation of thyroid hormone replacement during the course of the study. 16. Have a history of significant active or unstable major depressive disorder or other severe psychiatric disorder (e.g., schizophrenia, bipolar disorder) or other serious mood or anxiety disorder within the last 2 years Note: Participants with major depressive disorder or generalized anxiety disorder whose disease state is considered stable for the past 2 years and expected to remain stable throughout the course of the study, in the opinion of the investigator, may be considered for inclusion if they are not on excluded medications. 17. Have a PHQ-9 score of 15 or more during screening 18. Have acute suicidality, defined as endorsement of Item 4 and/or Item 5 of the Columbia-Suicide-Severity Scale (C-SSRS) at screening, or any condition that, in the judgment of the investigator, indicates a significant and immediate risk of suicide Note: The C-SSRS will only be assessed if PHQ-9 Item 9 is greater than 0 19. Have a history of lifetime suicidal behavior, defined as any positive response within the "Suicidal Behavior" section of the C-SSRS (except non-suicidal self-injurious behavior) Note: The C-SSRS will only be assessed if PHQ-9 Item 9 is greater than 0 20. Have acute or chronic hepatitis, signs and symptoms of any other liver disease other than metabolic dysfunction-associated fatty liver disease (MAFLD), or any of the following, as determined during screening: * Alanine aminotransferase (ALAT) level \>3.0x upper limit of normal (ULN) for the reference range * Total bilirubin (TBL) level \>1.5x ULN for the reference range (except for cases of known Gilbert's Syndrome) Note: If cholestatic liver disease is suspected, alkaline phosphatase level (ALP) must be \<1.5x ULN for the reference range. Note: Participants with MAFLD are eligible to participate in this trial if their ALAT level is ≤3.0x ULN for the reference range. 21. Have a family or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome Type 2 or a serum calcitonin level during screening of: * ≥20 ng/L, if eGFR ≥60 mL/min/1.73 m2, or * ≥35 ng/L, if eGFR \<60 mL/min/1.73 m2 22. Have a history of an active or untreated malignancy or are in remission from a clinically significant malignancy (other than basal or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer) for less than 5 years 23. Have a history of any other condition, such as known drug, alcohol, or substance abuse (including regular use of marijuana or tetrahydrocannabinol-containing products), a diagnosed eating disorder, or other psychiatric disorder, that, in the opinion of the investigator, may interfere with the participant's ability to comply with and/or complete the protocol 24. Have had a transplanted organ (other than corneal transplants \[keratoplasty\]) or awaiting an organ transplant 25. Have any clinically significant hematological condition that may interfere with accurate HbA1c measurement or interpretation (e.g., hemolytic anemias or sickle cell disease) 26. Have any other medical condition not listed above that, based on current clinical guidelines or in the opinion of the investigator, constitutes a contraindication to moderate-to-high intensity resistance training (e.g., active proliferative retinopathy, unstable musculoskeletal, neurological, or cardiovascular conditions, or other conditions associated with an increased risk of serious adverse events during resistance exercise) Prior/concomitant therapy 27. Have previously used a GLP-1 receptor agonist or a dual incretin receptor agonist at any time 28. Are currently receiving, or have received within 3 months prior to screening, chronic systemic glucocorticoid therapy (\>14 days), or have a clinically significant active autoimmune disease (e.g., lupus or rheumatoid arthritis) that, in the opinion of the investigator, requires or is likely to require systemic glucocorticoid treatment during the trial Note: Topical, intraocular, intranasal, intra-articular, or inhaled glucocorticoids are allowed 29. Have current or history of (within 3 months prior to screening) treatment with medications that may cause significant weight gain, including but not limited to, tricyclic antidepressants, atypical antipsychotics, and mood stabilizers Note: Selective serotonin reuptake inhibitors other than paroxetine are permitted. 30. Have taken, within 3 months prior to screening, medications (other than GLP-1 or dual GIP/GLP-1 receptor agonists) or alternative remedies that promote weight loss Note: Use of metformin or any other glucose-lowering medication, whether prescribed for polycystic ovary syndrome or diabetes prevention, is not permitted. Prior/concurrent clinical study / resistance training experience 31. Are currently enrolled in any other clinical study involving an IMP or any other type of medical research judged not to be scientifically or medically compatible with this clinical trial 32. Within the last 30 days of screening, have participated in a clinical trial and received treatment, whether active, or placebo. If the trial involved an IMP, 5 half-lives or 30 days, whichever is longer, should have passed. 33. Have participated in structured resistance training program (≥ 2x/week for ≥ 4 consecutive weeks) within the last 3 months Other exclusions 34. Have any contraindication to MRI (e.g., non-MRI-compatible implanted devices, metallic foreign bodies, severe claustrophobia, or body size exceeding MRI scanner limitations \[maximum bore diameter 70 cm\]) 35. Have a planned absence of ≥14 consecutive days (or a total of ≥ 30 days) within the next 6 months that would prevent adherence to scheduled trial visits and/or the training intervention