Effect of Semaglutide and Tirzepatide Combined With Exercise in Obesity

Comparison of the Effects of Semaglutide and Tirzepatide Treatments in Combination With Exercise in Obesity Management

Obesity is a growing global health problem that affects people of all ages. It can lead to serious health issues such as cardiovascular disease, insulin resistance, inflammation, and reduced physical function. New medications, including GLP-1 receptor agonists like semaglutide and dual GLP-1/GIP agonists like tirzepatide, have been shown to help people lose significant weight. However, some of this rapid weight loss may come from a reduction in muscle mass rather than fat. Losing muscle can lower physical performance, impair metabolic health, and increase the risk of developing sarcopenic obesity. This study aims to compare the effects of pharmacological treatment alone with a combined treatment program that includes both medication and exercise in individuals with obesity. The primary objective is to evaluate how these two approaches influence body composition.

The secondary objective is to examine the effects of pharmacological treatment versus combined treatment on cardiometabolic markers, peripheral muscle strength, functional capacity, respiratory function, respiratory muscle performance, and physical activity levels. The study seeks to determine whether adding structured exercise to medication can provide additional health benefits beyond weight loss.

Study Overview

• Status: Not yet recruiting
• Conditions: Obesity
• Intervention / Treatment: Drug: Semaglutide; Behavioral: Semaglutide+Exercise; Behavioral: Tirzepatide+Exercise; Drug: Tirzepatide

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Safak Yigit, PhD; Phone Number: +905309634910; Email: safak.yigit@galata.edu.tr

Study Locations

• Turkey (Türkiye)
  • Zeytinburnu
    • Istanbul, Zeytinburnu, Turkey (Türkiye)
      • Biruni University
      • Contact: Buket Akinci, Associate Professor, PhD; Phone Number: +905056415692; Email: bakinci@biruni.edu.tr
      • Sub-Investigator: Fulya Calikoglu, PhD
      • Sub-Investigator: Busra Ulker Eksi, PhD
      • Sub-Investigator: Alihan Oral, PhD
      • Sub-Investigator: Buket Akinci, PhD
      • Principal Investigator: Safak Yigit, PhD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Those between the ages of 25 and 60 years
• Those with a body mass index (BMI) between 30 and 40 kg/m2 according to the World Health Organization (WHO) classification
• Individuals who volunteered to participate in the study

Exclusion Criteria:

• Individuals with a BMI greater than 40 kg/m2 according to the WHO classification
• Individuals with a Charlson comorbidity index score of 3 or higher
• Uncontrolled arrhythmia, hypertension, heart failure, diabetes, and unstable angina pectoris
• Cooperation impairment, orthopedic, and neurological problems that may interfere with evaluation and treatment
• Individuals with a history of lower extremity injury or surgery in the last six months
• Diagnosed with diabetes and complications such as nephropathy, retinopathy, and neuropathy
• Individuals with concomitant chronic respiratory disease
• Individuals with acute infections
• Individuals with middle ear pathologies (such as tympanic membrane rupture, otitis media)
• Individuals with a history of spontaneous or trauma-related pneumothorax
• Smokers
• Pregnancy
• Individuals with a STOP-bang score of 3 or higher
• Individuals on a structured diet program for weight loss during the study period
• Individuals who have had endoscopic intervention and/or bariatric surgery within the last year

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ARM 1-Semaglutide; Drug: Semaglutide	Drug: Semaglutide; They will use only semaglutide.
Experimental: ARM 3-Semaglutide + Exercise	Behavioral: Semaglutide+Exercise; This group will engage in exercise and receive semaglutide therapy."
Experimental: ARM 4-Tirzepatide + Exercise	Behavioral: Tirzepatide+Exercise; This group will engage in exercise and receive tirzepatide therapy."
Experimental: ARM 2-Tirzepatide; Drug: Tirzepatide	Drug: Tirzepatide; They will use only tirzepatide.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body fat-muscle ratios (Body composition)	These measurements will be determined by bioelectrical impedance.	Three months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peripheral muscle strength	M. Quadriceps muscle strength and hand grip strength measurement will be used to evaluate peripheral muscle strength (kg). Hand-held dynamometer will be used to evaluate quadriceps muscle strength and hand grip strength (kg).	Three months
Glucose profile	Glucose profile after 12 hours of fasting will be measured. (mg/dL)	Three months
Functional capacity	Submaximal functional exercise capacity of the participants will be evaluated with the six-minute walk test.	Three months
Pulmonary function	Spirometric assessment will be performed to determine participants' forced expiratory volume in one second (FEV1). Spirometric assessment will be performed to determine participants' forced vital capacity (FVC).	Three months
Respiratory muscle strength	Respiratory muscle strength; It will be evaluated with an intraoral pressure measuring device in a sitting position.	Three months
Physical activity level	Step Count Measurement: Daily step count will be monitored to determine the physical activity level of the participants. Step count will be assessed with a wearable activity monitor, a portable, easy-to-use tool that can measure objectively (Huawei Watch Fit Special Edition). With its six-axis sensor, the device records the user's physical activity style information in its temporary memory throughout the duration of use. Participants will be asked to wear the activity monitor on their left wrist throughout and only remove it during bathing. After one week of use, the data recorded with the wearable activity monitor will be taken.	Three months
Incremental load test (Respiratory Muscle Endurance)	Respiratory muscle endurance will be evaluated by incremental load test. The incremental load test will be performed using the electronic inspiratory loading device (PowerBreathe®-KHP2).	Three months
Lipid Profile	Lipid profile after 12 hours of fasting will be measured	Three months

Collaborators and Investigators

• Sponsor: Istanbul Galata University
• Collaborators: Istanbul University; Biruni University

Study record dates

Study Major Dates

• Study Start (Estimated): December 29, 2025
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: December 7, 2025
• First Submitted That Met QC Criteria: December 21, 2025
• First Posted (Actual): January 6, 2026

Study Record Updates

• Last Update Posted (Actual): January 6, 2026
• Last Update Submitted That Met QC Criteria: December 21, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Amino Acids, Peptides, and Proteins; Proteins; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide; Tirzepatide; semaglutide
• Other Study ID Numbers: 2025-GLP1-OBESITY

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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