Resistance Training to Prevent Muscle Loss During Treatment With Tirzepatide

NCT07777575 | Recruiting Phase 4

• 2 other identifiers: RESIST-26-HAL-0150-I2026-526200-69-00
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

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'.

Conditions

Obesity (BMI>30)

Keywords

skeletal muscle; weight loss; exercise training; strength training; incretin-based therapy

Outcome Measures

Primary Outcomes (1)

• Change in contractile thigh muscle volume (mL), as assessed by magnetic resonance imaging (MRI)

  From baseline to the end of treatment at 24 weeks

Secondary Outcomes (21)

• Change in body weight (kg), as assessed by a calibrated scale

  From baseline to the end of treatment at 24 weeks

• Change in anterior thigh intramuscular fat fraction (%), as assessed by MRI

  From baseline to the end of treatment at 24 weeks

• Change in contractile muscle volume of the combined scapular and upper back musculature (mL), as assessed by MRI

  From baseline to the end of treatment at 24 weeks

• Change in combined whole-trunk and thigh fat volume (mL), as assessed by MRI

  From baseline to the end of treatment at 24 weeks

• Change in peak isometric knee extension torque (Nm), as assessed using an isokinetic dynamometer

  From baseline to the end of treatment at 24 weeks

Study Arms (2)

Dual GIP/GLP-1 Receptor Agonist Tirzepatide

ACTIVE COMPARATOR

Drug: Dual GIP/GLP-1 Receptor Agonist Tirzepatide

Dual GIP/GLP-1 Receptor Agonist Tirzepatide + Resistance Training

EXPERIMENTAL

Drug: Dual GIP/GLP-1 Receptor Agonist Tirzepatide; Behavioral: Resistance Training

Interventions

Dual GIP/GLP-1 Receptor Agonist Tirzepatide DRUG

Tirzepatide will be titrated to a maximum tolerated dose of up to 10 mg/week (+2.5 mg/week every 4 weeks) and accomponied by regular individual diet and physical activity counseling

Dual GIP/GLP-1 Receptor Agonist Tirzepatide; Dual GIP/GLP-1 Receptor Agonist Tirzepatide + Resistance Training

Resistance Training BEHAVIORAL

Low-volume, high-intensity resistance training on 3 days/week

Dual GIP/GLP-1 Receptor Agonist Tirzepatide + Resistance Training

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age
• Are ≥ 18 years and ≤ 60 years of age
• Weight
• Have a body mass index (BMI) of ≥ 30 kg/m2
• Have a history of at least 1 self-reported unsuccessful dietary effort to lose body weight
• 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 \[only for women\]
• 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.

You may not qualify if:

• Medical Conditions Diabetes Related
• 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
• 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
• Have a self-reported reduction in body weight \>5 kg within 3 months prior to screening
• Have a prior or planned surgical treatment for obesity (excluding liposuction or abdominoplasty if performed \>1 year prior to screening)
• 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)
• 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
• Are currently breastfeeding
• Have structural cardiovascular disease (e.g., ischemic cardiovascular disease, heart failure, previous cerebrovascular accident \[stroke\])
• Have atrial fibrillation
• Have uncontrolled hypertension (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg)

Sponsors & Collaborators

• Technical University of Munich: lead
• EGYM SE: collaborator

Study Sites (1)

Klinikum der Technischen Universität München (TUM Klinikum)

München, Bavaria, 80809, Germany

RECRUITING

MeSH Terms

Conditions

Obesity; Weight Loss

Interventions

Resistance Training

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Body Weight Changes

Intervention Hierarchy (Ancestors)

Exercise Therapy; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Physical Therapy Modalities; Physical Conditioning, Human; Exercise; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Martin Halle, MD

  Klinikum der Technischen Universität München (TUM Klinikum)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stephan Mueller-Stegner, Dr rer nat

CONTACT

+49 (0)89 289-24494; stephan.mueller@mri.tum.de

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Acquisition and image analysis of the MRI based endpoints, including the primary endpoint, will be performed by personnel blinded to group allocation. Wherever possible, analysis of additional secondary endpoints will be conducted blinded to group allocation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2026
• First Posted: August 20, 2026
• Study Start: September 7, 2026
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2027
• Last Updated: September 17, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)