Tirzepatide and Muscle Outcomes in Obesity (TIRMO)

January 23, 2026 updated by: University Medical Centre Ljubljana

Effects of Tirzepatide on Skeletal Muscle in Obesity

This study is evaluating whether a dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, tirzepatide, can affect the function, structure and metabolism of skeletal muscles in adults with obesity. Participants, premenopausal females with obesity, will receive either tirzepatide or placebo over 24 weeks. Researchers will assess body weight, body composition, muscle strength and functional performance, neuromuscular function and will perform muscle biopsies before and after treatment to study molecular and histological changes following treatment. The goal of this study is to investigate the effects of tirzepatide on skeletal muscle function, quantity, quality and metabolism in adults with obesity as well as clarify the molecular and structural adaptations in skeletal muscle during tirzepatide-induced weight loss, addressing an important gap in understanding the impact of incretin-based therapies on muscle health.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Slovenia
      • Ljubljana, Slovenia, 1000
        • Recruiting
        • Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana
        • Contact:
        • Principal Investigator:
          • Prof. Mojca Jensterle Sever, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Female sex
  • Age between 18 and 50 years
  • BMI between 30 kg/m² and 40 kg/m²
  • Stable body weight within the three months preceding study enrolment (defined as ≤ 5% change)
  • No prior pharmacological or surgical interventions for obesity treatment
  • Commitment to use barrier contraception and absence of plans for pregnancy within 8 months following enrolment

Exclusion Criteria:

  • Sarcopenic obesity
  • Pregnancy or lactation
  • Postmenopausal status
  • Diabetes
  • Immobility
  • Personal history of malignancy
  • Personal history of pancreatitis
  • Personal history of major depressive episodes
  • Personal history of myopathy
  • Personal or family history of medullary thyroid carcinoma
  • Current treatment with metformin or systemic corticosteroids

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo
Drug: Placebo
Placebo (saline solution) will be administered via subcutaneous injection once weekly with dose escalation following the same schedule (2.5 mg equivalent increments every 4 weeks) to preserve blinding integrity.
Experimental: Tirzepatide
Drug: Tirzepatide
Tirzepatide is a dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist. It will be administered via subcutaneous injection once weekly in a dose-titration scheme: starting at 2.5 mg and increased every 4 weeks by 2.5 mg up to a maximum of 15 mg, based on tolerability.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in Body Mass and Composition
Time Frame: Baseline to Week 24
Measured primarily as changes in body weight and body composition measured by dual-energy X-ray absorptiometry (DXA).
Baseline to Week 24
Change in Quadriceps Muscle Strength
Time Frame: Baseline to Week 24
Change in maximal knee extensor torque normalized to body mass (Nm/kg) will be evaluated using an isokinetic dynamometer.
Baseline to Week 24

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in MRI-derived Skeletal Muscle Composition and Myosteatosis
Time Frame: Baseline to Week 24
Muscle volume and muscle fat fraction will be quantified using magnetic resonance imaging (MRI).
Baseline to Week 24
Change in Molecular Markers in Vastus Lateralis Muscle: Gene-level Differential Expression
Time Frame: Baseline to Week 24
Transcriptome-wide RNA-sequencing will be performed on vastus lateralis muscle biopsies from all participants (depending on sample quality and RNA integrity) before and after the intervention to identify differentially expressed genes associated with tirzepatide treatment. Differential gene expression will be reported as log2 fold change (log2FC) between post and pre-intervention, derived from normalized RNA-sequencing read counts. Statistical significance will be summarized using false discovery rate (FDR)-adjusted p-values.
Baseline to Week 24
Change in Molecular Markers in Vastus Lateralis Muscle: Pathway-level Enrichment Analysis
Time Frame: Baseline to Week 24
Pathway-level changes will be reported using normalized enrichment scores (NES) derived from gene set enrichment analysis (GSEA), together with false discovery rate (FDR)-adjusted q-values for biological processes including mitochondrial function, lipid metabolism, insulin signaling, inflammation, muscle atrophy, and myogenesis.
Baseline to Week 24
Change in Intramyocellular Lipid Content (IMCL) in Vastus Lateralis Muscle
Time Frame: Baseline to Week 24
Assessed by Oil Red O staining using a standard protocol. IMCL will be quantified as the proportion of Oil Red O-positive area per fibre and averaged across available fibres per section per time point. Microscopy imaging and analysis settings will be kept consistent across time points, and assessors will be blinded to group/time.
Baseline to Week 24
Change in the Muscle Fiber Diameter of Type I and Type II Fibers
Time Frame: Baseline to Week 24
Muscle fiber diameter will be measured on the biopsy section using routine light microscopy. Fiber typing (type 1 vs type 2) will be performed by standard immunohistochemistry for myosin heavy chain isoforms. The metric is mean minimal Feret diameter in micrometers, averaged across available fibers of same type.
Baseline to Week 24

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in Handgrip Strenght
Time Frame: Baseline to Week 24
Change in maximal handgrip strength, normalized to body mass, will be assessed using a handheld dynamometer.
Baseline to Week 24
Changes in Lower-Limb Functional Performance
Time Frame: Baseline to Week 24
Change in lower-limb functional performance assessed using standardized sit-to-stand testing.
Baseline to Week 24
Change in 6-Minute Walk Test (6MWT)
Time Frame: Baseline to Week 24
The six-minute walk test (6MWT) will be used to assess functional exercise capacity. The outcome will be the total distance walked (meters) over 6 minutes on a flat corridor, following standardized guidelines.
Baseline to Week 24
Spatial Transcriptomics Analysis of Vastus Lateralis Muscle Biopsy Samples
Time Frame: Baseline to Week 24
Potential exploratory: Feasibility-dependent analysis of spatial transcriptomic profiles in skeletal muscle biopsy. The objective is to identify treatment-related changes in spatial gene expression patterns in skeletal muscle tissue sections. A subset of approximately 8 patients (paired pre- and post-treatment muscle biopsy samples) will be selected for downstream analyses based on transcriptomic profiles obtained from the full RNA-seq dataset.
Baseline to Week 24
Electrophysiological Assessment of Motor Responses in Skeletal Muscles
Time Frame: Baseline to Week 24
Potential exploratory: Electrophysiological recordings of motor responses (compound muscle action potentials, CMAP) will be assessed to evaluate potential changes in peripheral motor nerve excitability and neuromuscular function.
Baseline to Week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Medical Centre Ljubljana

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Mojca Jensterle Sever, Prof.MD, PhD, Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 5, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 23, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 28, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 28, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 23, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • TIRMO-0120-121/2025-2711-6

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

De-identified individual participant data (IPD) to be shared will include demographic data, basic clinical measurements, body composition assessment, laboratory results, muscle strength and function assessment data, molecular data and histological features from skeletal muscle biopsies. All shared data will be fully de-identified, and no directly identifiable personal information will be included.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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