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NCT Number: NCT07609160

Effectiveness of Combined GLP-1/GIP Dual Agonist Therapy and Structured Exercise on Skeletal Muscle Morphology, Quality, and Physical Function in Overweight and Obese Individuals

This randomized controlled trial aims to investigate the effects of a 24-week home-based progressive resistance exercise program combined with tirzepatide treatment on skeletal muscle mass, muscle quality, and functional capacity in overweight and obese individuals. A total of 108 participants initiating tirzepatide therapy will be randomized to either exercise plus pharmacotherapy or pharmacotherapy alone. The primary outcome is change in thigh muscle thickness and echo intensity assessed by ultrasonography.

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Key information

About this study

Pharmacologically induced weight loss with glucagon-like peptide-1 (GLP-1)/ glucose-dependent insulinotropic polypeptide (GIP) receptor agonists such as tirzepatide is associated with significant reductions in lean body mass, raising concerns regarding muscle function and long-term outcomes. Resistance exercise is the most effective intervention to preserve muscle mass during weight loss; however, evidence combining these approaches is limited.

This study is a prospective, two-center, single-blinded, randomized controlled trial designed to evaluate whether structured resistance exercise enhances muscle preservation and functional outcomes in individuals receiving tirzepatide therapy.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • initiation of tirzepatide-based pharmacological treatment as prescribed by an endocrinology and metabolism specialist,
  • body mass index (BMI) ≥27 kg/m² and the presence of a comorbidity condition or BMI≥30 kg/m²
  • age between 18 and 65 years

Exclusion criteria

  • diagnosis of type 1 or type 2 diabetes mellitus
  • presence of cerebrovascular, hematological, pulmonary, rheumatological, or neurological disorders
  • current participation in a structured diet or exercise program
  • use of weight-loss medications within the past 12 months
  • history of upper or lower extremity surgery or injury within the past 6 months
  • any contraindication to resistance exercise as determined by the treating physician.

Treatment and study plan

Resistance Exercise

Other

A 24-week home-based resistance exercises using elastic band and bodyweight

Lifestyle Recommendations

Other

Lifestyle recommendations including physical activity and nutritional advice

Primary outcomes

  1. Change in muscle thickness

    Time frame: Baseline, 12 weeks, 24 weeks

    Muscle thickness of the thigh (quadriceps femoris) will be assessed using a portable ultrasound and will be presented in millimeters (mm).

  2. Muscle echo intensity

    Time frame: Baseline, 12 weeks, 24 weeks

    Echo intensity will be assessed via a portable muscle ultrasonography using grayscale analysis (0-255 scale) within a standardized region of interest using ImageJ software (National Institutes of Health, USA), with higher values indicating greater intramuscular fat and fibrous tissue infiltration and thus poorer muscle quality. Assessments will include quadriceps femoris.

Secondary outcomes

  1. Muscle strength (handheld dynamometer)

    Time frame: Baseline, 12 weeks, 24 weeks

    Isometric muscle strength of the biceps brachii, triceps brachii, quadriceps femoris, and hamstrings will be assessed bilaterally using a Lafayette handheld dynamometer (Lafayette Instrument Company®, USA) using the make test method.

  2. Body weight

    Time frame: Baseline, 12 weeks, 24 weeks

    Body weight will be assessed using bioelectrical impedance analysis and presented in kilograms (kg).

  3. Six-minute walk test

    Time frame: Baseline, 12 weeks, 24 weeks

    Functional capacity will be assessed using the 6-minute walk test according to standardized procedures and the total distance will be recorded in meters.

  4. Physical activity

    Time frame: Baseline, 12 weeks, 24 weeks

    Physical activity will be measured objectively using a wearable device (Garmin Vívosmart 5), time spent for light, moderate, and vigorous activity will be recorded for 7 days.

  5. Nutritional status (3-day food record)

    Time frame: Baseline, 12 weeks, 24 weeks

    Dietary intake will be assessed at baseline, 12 weeks, and 24 weeks using 3-day food records (two non-consecutive weekdays and one weekend day). Prior to assessment, participants will receive standardized verbal, written, and visual instructions - including portion size estimation aids - to ensure accurate and consistent recording.

  6. Quality of life (Short Form-36)

    Time frame: Baseline, 12 weeks, 24 weeks

    The Short Form-36, a validated and reliable self-reported instrument evaluating physical and mental health status across eight domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health will be used to determine the level of quality of life. Physical and mental sub scales are scored from 0 to 100, higher scores indicate a better quality of life.

  7. Clinical parameters (blood pressure)

    Time frame: Baseline, 12 weeks, 24 weeks

    Blood pressure will be measured using a sphygmomanometer at each assessment point.

  8. Height

    Time frame: Baseline, 12 weeks, 24 weeks

    Height of the participants will be assessed using a stadiometer and presented in meters.

  9. Body mass index

    Time frame: Baseline, 12 weeks, 24 weeks

    Body mass index will be calculated using height and weight (kg/m^2)

  10. Body fat percentage

    Time frame: Baseline, 12 weeks, 24 weeks

    Body fat percentage will be assessed using bioelectrical impedance analysis and presented in percentage (%).

  11. Fat free mass

    Time frame: Baseline, 12 weeks, 24 weeks

    Fat-free mass will be assessed using bioelectrical impedance analysis and presented in kilograms.

  12. Chair stand test

    Time frame: Baseline, 12 weeks, 24 weeks

    Functional capacity will be assessed using 30-second chair stand test according to standardized procedures. The number of repetitions which the participants fully raised from a chair will be recorded in numbers (n).

  13. Self-reported physical activity

    Time frame: Baseline, 12 weeks, 24 weeks

    Self-reported physical activity will be determined using the International Physical Activity Questionnaire-Short Form (IPAQ-SF). Metabolic equivalent (MET) values will be calculated and participants will be categorized into inactive, moderately active, and very active based on MET values.

  14. Grip strength

    Time frame: Baseline, 12 weeks, 24 weeks

    Handgrip strength will be assessed using a JAMAR dynamometer (Sammons Preston, USA) following the standardized protocol. Three maximal isometric contractions will be performed with 1-minute rest intervals, the mean of the three trials in kilograms will be used for analysis.

  15. Clinical measures (fasting glucose)

    Time frame: Baseline, 12 weeks, 24 weeks

    Fasting glucose will be recorded from the medical records and will be presented in mmol/L.

  16. Clinical parameters (lipid profile)

    Time frame: Baseline, 12 weeks, 24 weeks

    Total Cholesterol, LDL (Low-Density Lipoprotein) Cholesterol, HDL (High-Density Lipoprotein) Cholesterol, Triglycerides will be recorded from the medical records and presented in mmol/L.

  17. Muscle thickness

    Time frame: Baseline, 12 weeks, 24 weeks

    Muscle thickness of the biceps femoris, triceps brachii, and biceps brachia will be assessed using a portable ultrasound and will be presented in millimeters (mm).

  18. Muscle echo intensity

    Time frame: Baseline, 12 weeks, 24 weeks

    Echo intensity will be assessed via a portable muscle ultrasonography using grayscale analysis (0-255 scale) within a standardized region of interest using ImageJ software (National Institutes of Health, USA), with higher values indicating greater intramuscular fat and fibrous tissue infiltration and thus poorer muscle quality. Assessments will include biceps femoris, biceps brachii, and triceps brachii.

Study contacts

Contact information is provided by the study sponsor or research team.

Özgül Öztürk, Associate Professor

CONTACT

[email protected]

902165004185

Sponsors and collaborators

Lead sponsor

Acibadem University

Other

Registry information

Official study title

Effectiveness of Combined GLP-1/GIP Dual Agonist Therapy and Structured Exercise on Skeletal Muscle Morphology, Quality, and Physical Function in Overweight and Obese Individuals: a Randomized Controlled Trial Protocol

Important dates

Study start
2026
Primary completion
2027
Study completion
2028
First posted
May 27, 2026
Registry last updated
Jun 4, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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