Tirzepatide and Muscle Outcomes in Obesity
ConditionObesity (Disorder)
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexFemale
Age18-50
SponsorUniversity Medical Centre Ljubljana
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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)
Disqualifiers
Sarcopenic obesity
Pregnancy or lactation
Postmenopausal status
Diabetes
Trial design
Design model
Parallel
Treatments tested in this trial
Tirzepatide
DrugTirzepatide 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.
Placebo
DrugPlacebo (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.
Treatment groups
30 Participants
are divided into 2 treatment groupsGroup A: TirzepatideExperimental treatment 1 intervention
Group B: PlaceboPlacebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
Change in Body Mass and Composition
Measured primarily as changes in body weight and body composition measured by dual-energy X-ray absorptiometry (DXA).
Time frame
Baseline to Week 242
Change in Quadriceps Muscle Strength
Change in maximal knee extensor torque normalized to body mass (Nm/kg) will be evaluated using an isokinetic dynamometer.
Time frame
Baseline to Week 24Secondary outcomes
1
Change in MRI-derived Skeletal Muscle Composition and Myosteatosis
Muscle volume and muscle fat fraction will be quantified using magnetic resonance imaging (MRI).
Time frame
Baseline to Week 242
Change in Molecular Markers in Vastus Lateralis Muscle: Gene-level Differential Expression
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.
Time frame
Baseline to Week 243
Change in Molecular Markers in Vastus Lateralis Muscle: Pathway-level Enrichment Analysis
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.
Time frame
Baseline to Week 244
Change in Intramyocellular Lipid Content (IMCL) in Vastus Lateralis Muscle
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.
Time frame
Baseline to Week 24Other outcomes
1
Change in Handgrip Strenght
Change in maximal handgrip strength, normalized to body mass, will be assessed using a handheld dynamometer.
Time frame
Baseline to Week 242
Changes in Lower-Limb Functional Performance
Change in lower-limb functional performance assessed using standardized sit-to-stand testing.
Time frame
Baseline to Week 243
Change in 6-Minute Walk Test (6MWT)
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.
Time frame
Baseline to Week 244
Spatial Transcriptomics Analysis of Vastus Lateralis Muscle Biopsy Samples
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.
Time frame
Baseline to Week 24Sponsors and contacts
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Source ClinicalTrials.gov