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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Obesity; Sarcopenia; Overweight (Without Type 2 Diabetes) With Weight-related Comorbidities
• Intervention / Treatment: Other: Resistance exercise; Other: Lifestyle recommendations

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 108
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Özgül Öztürk, Associate Professor; Phone Number: 902165004185; Email: ozgul.ozturk@acibadem.edu.tr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Resistance Exercise + Tirzepatide; 24-week home-based progressive resistance exercise program (3 sessions/week) using elastic bands and bodyweight exercises, combined with tirzepatide treatment and general lifestyle recommendations..	Other: Resistance exercise; A 24-week home-based resistance exercises using elastic band and bodyweight; Other: Lifestyle recommendations; Lifestyle recommendations including physical activity and nutritional advice
Active Comparator: Tirzepatide Alone; Standard tirzepatide treatment with usual care and general lifestyle recommendations.	Other: Lifestyle recommendations; Lifestyle recommendations including physical activity and nutritional advice

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in muscle thickness	Muscle thickness of the thigh (quadriceps femoris, hamstrings), gastrocnemius, biceps brachii and triceps brachii will be assessed using a portable ultrasound and will be presented in millimeters (mm).	Baseline, 12 weeks, 24 weeks
Muscle echo intensity	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 four muscle groups: biceps brachii, triceps brachii, quadriceps femoris, and biceps femoris.	Baseline, 12 weeks, 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle strength (handheld dynamometer)	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.	Baseline, 12 weeks, 24 weeks
Body weight	Body weight will be assessed using bioelectrical impedance analysis and presented in kilograms (kg).	Baseline, 12 weeks, 24 weeks
Six-minute walk test	Functional capacity will be assessed using the 6-minute walk test according to standardized procedures and the total distance will be recorded in meters.	Baseline, 12 weeks, 24 weeks
Physical activity	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.	Baseline, 12 weeks, 24 weeks
Nutritional status (3-day food record)	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.	Baseline, 12 weeks, 24 weeks
Quality of life (Short Form-36)	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.	Baseline, 12 weeks, 24 weeks
Clinical parameters (blood pressure)	Blood pressure will be measured using a sphygmomanometer at each assessment point.	Baseline, 12 weeks, 24 weeks
Height	Height of the participants will be assessed using a stadiometer and presented in meters.	Baseline, 12 weeks, 24 weeks
Body mass index	Body mass index will be calculated using height and weight (kg/m^2)	Baseline, 12 weeks, 24 weeks
Body fat percentage	Body fat percentage will be assessed using bioelectrical impedance analysis and presented in percentage (%).	Baseline, 12 weeks, 24 weeks
Fat free mass	Fat-free mass will be assessed using bioelectrical impedance analysis and presented in kilograms.	Baseline, 12 weeks, 24 weeks
Chair stand test	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).	Baseline, 12 weeks, 24 weeks
Self-reported physical activity	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.	Baseline, 12 weeks, 24 weeks
Grip strength	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.	Baseline, 12 weeks, 24 weeks
Clinical measures (fasting glucose)	Fasting glucose will be recorded from the medical records and will be presented in mmol/L.	Baseline, 12 weeks, 24 weeks
Clinical parameters (lipid profile)	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.	Baseline, 12 weeks, 24 weeks

Collaborators and Investigators

• Sponsor: Acibadem University

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: April 28, 2026
• First Submitted That Met QC Criteria: May 21, 2026
• First Posted (Actual): May 27, 2026

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: physical activity; exercise; muscle; physical function
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Neuromuscular Manifestations; Nutrition Disorders; Pathological Conditions, Anatomical; Overnutrition; Body Weight; Muscular Atrophy; Atrophy; Pathological Conditions, Signs and Symptoms; Behavior; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; Sarcopenia; Motor Activity; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Therapeutics; Physical Therapy Modalities; Patient Care; Exercise Therapy; Rehabilitation; Aftercare; Continuity of Patient Care; Physical Conditioning, Human; Exercise; Resistance Training
• Other Study ID Numbers: Özgül Öztürk; Grant proposal submitted (Other Identifier: Acıbadem University)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) will not be shared. The study data contains personal health information. Also, data sharing may also be limited by institutional policies and data protection legislation. Findings will be reported in aggregate form.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No