Function and Lean Mass Preservation With Resistance Exercise During a GLP-1RA Treatment

NCT07457437 | Recruiting DMC

• 1 other identifier: 11468874
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to investigate the effect that a structured, progressive resistance exercise program may have on maintaining the muscle mass and physical function of overweight/ obese females whilst they experience a tirzepatide (GLP-1/GIP receptor agonist) induced weight loss. Overweight and obese females aged 25-50 will be recruited for the study, they will require a BMI of \>30 or \>27 with one obesity related comorbidity (excluding diabetes). They will be screened, prescribed tirzepatide and then randomly assigned to either the intervention (GLP-1/GIP + Exercise) or the control group (GLP-1/GIP). Groups will then be split into pre and peri menopausal groups to provide a further exploratory pathway looking analysing if the menopause transition may have any effect on our outcome variables. This was proposed as in the UK females are more likely to begin GLP-1RA treatment. Both groups will be given an industry standard treatment of tirzepatide over 20 weeks starting at a dose of 2.5mg/week and following the dose titration process of +2.5mg/week every four weeks outlined by its manufacturers. The Exercise Group (GLP-1 +EXC) will be given the same tirzepatide prescription alongside following a progressive resistance exercise program. The exercise program will follow a similar structure to previous work in which participants will complete a propriety 20-wk whole body, low impact resistance exercise training program four times a week. The exercise sessions will be up to an hour and will be instructor lead by video and supervised by a member of the research team at The University of Exeter.

Conditions

Physical Function; Muscle Mass and Strength; Obesity & Overweight

Keywords

Maintaining muscle mass on GLP-1RA, physical function on GLP-1RA, tirzepatide, Mounjaro,; Body composition changes during GLP-1/GIP RA weight loss; Resistance exercise and Perimenopause; Lean mass and Tirzepatide; Health outcomes and obesity

Outcome Measures

Primary Outcomes (2)

• Skeletal Muscle Mass

  Muscle Mass via (D3-Creatine). Skeletal muscle mass will be measured by the stable isotope labelled tracer creatine technique using methyl-\[D3\]-creatine (D3-Cr) to quantify whole-body skeletal muscle mass. A fasted urine sample will be collected after which a 30mg of D3-Cr will be administered at hr 0s. Total 24 hr urine volume output will be collected by the participant and returned to laboratory for analysis. Single urine samples will also be collected at 48 and 72 hrs after D3-Cr ingestion.

  Skeletal muscle mass will be plotted over time and we will compare the pre , mid and post values (weeks 0, 10 and 20) to see if there was a change in both groups.

• Muscle Thickness (Ultrasound)

  Vastus lateralis and Bicep Brachi muscle thickness will be measured in the longitudinal and crosssectional plane via a 7.7-Hz linear transducer, using B-mode ultrasonography (Vscan Air; GE Healthcare, Chalfont St Giles, UK). Three images will be acquired at each site and analyzed using ImageJ v1.53t (National Institutes of Health, Bethesda, MD) software after being scaled from pixels to cm.

  Muscle thickness in millimetres will be plotted over time (week 0, 4, 8, 10, 12, 16, 20) and compared between the two groups. Muscle thickness will also be measure at two separate time points during a follow up study at week 40 and 72 weeks from week 0.

Secondary Outcomes (13)

• Isokinetic dynamometry (Bicep and Quadriceps) Peak Torque (Nm/kg)

  Peak torque in Nm/kg will be compared between pre, mid and post (weeks 0, 10 and 20) in both groups and plotted against time. As well as during follow ups at weeks 40 and 72

• Isokinetic Dynamometry (Quadriceps and Bicep) Fatigue Profile (%)

  Fatigue profile (%) will be compared between pre, mid and post (weeks 0, 10 and 20) in both groups and plotted against time. As well as during follow ups at weeks 40 and 72

• Physical Function 60 second sit-to-stand test

  Sit to stand scores will be compared between groups and pre, mid and post intervention (weeks 0, 10 and 20). The measured again at follow up visits in week 40 and 72.

• Dynamic Balance, Y-balance Test

  Balance test scores will be compared between groups and at pre, mid and post intervention (weeks 0, 10 and 20). Then again at follow up visits at weeks 40 and 72.

• Handgrip dynamometry

  Grip strength scores will be compared between groups and pre, mid and post intervention (weeks 0, 10 and 20). Then again at follow up visits at weeks 40 and 72

Other Outcomes (4)

• Quality of Life Short Form 36

  The SF-36 will be completed remotely on weeks 0, 10 and 20.

• The Pittsburgh Sleep Quality Index (PSQI)

  The PSQI will be completed remotely on weeks 0, 10 and 20.

• Habitual physical activity (MET)

  Physical activity will be measured on week 0, 10 and 20.

Study Arms (2)

GLP-1RA+EXERCISE

EXPERIMENTAL

In the resistance exercise arm participants will undergo a 20 week resistance exercise program. This will be s supervised in person session 4 times a week.

Other: Progressive Resistance Exercise Training Program

GLP-1RA

PLACEBO COMPARATOR

Habitual physical activity guidelines

Other: Habitual physical activity guidelines

Interventions

Progressive Resistance Exercise Training Program OTHER

Participants in the GLP-1 + Exc group will participate in a 20 Week Progressive Resistance Exercise Training Program. This will be a low impact training program created by PVolve LLC. The plan will increase in session frequency and volume reaching 4 sessions per week at week 4 up until week 20 and will comprise of mostly banded, weighted or bodyweight exercises with small high intensity interval sessions after some of the sessions. Participants will attend the exercise classes on site at the St Luke's campus which will be delivered by PVolve instructors via video demonstration. Classes will be supervised by a member of the research team at all times.

GLP-1RA+EXERCISE

Habitual physical activity guidelines OTHER

Control group consisting of continuing habitual physical activity guidelines for 20 weeks

GLP-1RA

Eligibility Criteria

• Age: 25 Years - 50 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• years old
• BMI ≥27 kg/m2 with one obesity related co-morbidity or a BMI between ≥30 and 35 kg/m2
• Female

You may not qualify if:

• Previous GLP-1RA use
• Diabetes (Type 1 and 2)
• Contraindicative health condition to GLP-1/GIP
• Fail clinically administered health screening form for tirzepatide prescription
• Pregnant or wanting to become pregnant in the next 6 months
• Has or has previously had an eating disorder
• Inability to perform exercise program and exercise tests
• Advised not to exercise by their general practitioner or medical professional
• Current or recent injury within the last 6 months that may affect the ability to carry out resistance exercise
• Has consistently resistance trained previously (\>10 sessions per year)
• Currently taking medication or supplements that have been shown to impact muscle function and muscle mass in the last 6 months
• Current or recent, ≤6 months, smoker
• Currently on HRT

Sponsors & Collaborators

• University of Exeter: lead

Study Sites (1)

Nutritional Physiology Research Unit

Exeter, Devon, EX2 4TH, United Kingdom

RECRUITING

Related Publications (5)

• Svensen E, Koscien CP, Alamdari N, Wall BT, Stephens FB. A Novel Low-Impact Resistance Exercise Program Increases Strength and Balance in Females Irrespective of Menopause Status. Med Sci Sports Exerc. 2025 Mar 1;57(3):501-513. doi: 10.1249/MSS.0000000000003586. Epub 2024 Nov 6.

  PMID: 39480197 BACKGROUND

• Verreijen AM, Engberink MF, Memelink RG, van der Plas SE, Visser M, Weijs PJ. Effect of a high protein diet and/or resistance exercise on the preservation of fat free mass during weight loss in overweight and obese older adults: a randomized controlled trial. Nutr J. 2017 Feb 6;16(1):10. doi: 10.1186/s12937-017-0229-6.

  PMID: 28166780 BACKGROUND

• Look M, Dunn JP, Kushner RF, Cao D, Harris C, Gibble TH, Stefanski A, Griffin R. Body composition changes during weight reduction with tirzepatide in the SURMOUNT-1 study of adults with obesity or overweight. Diabetes Obes Metab. 2025 May;27(5):2720-2729. doi: 10.1111/dom.16275. Epub 2025 Feb 25.

  PMID: 39996356 BACKGROUND

• Sargeant JA, Henson J, King JA, Yates T, Khunti K, Davies MJ. A Review of the Effects of Glucagon-Like Peptide-1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors on Lean Body Mass in Humans. Endocrinol Metab (Seoul). 2019 Sep;34(3):247-262. doi: 10.3803/EnM.2019.34.3.247.

  PMID: 31565876 BACKGROUND

• Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang S, Liu B, Bunck MC, Stefanski A; SURMOUNT-1 Investigators. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022 Jul 21;387(3):205-216. doi: 10.1056/NEJMoa2206038. Epub 2022 Jun 4.

  PMID: 35658024 BACKGROUND

MeSH Terms

Conditions

Obesity; Overweight

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Francis B Stephens, PhD

  University of Exeter

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Thomas P J Kennedy, MSc

CONTACT

+44 7470074405; tk509@exeter.ac.uk

Sarah K Graham, MSc

CONTACT

+44 7789552977; sg1034@exeter.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: This study will be a randomised, longitudinal, parallel group study design. It will show if a progressive resistance exercise program will be superior in maintaining muscle mass and physical function in overweight/obese females whilst undertaking a 20-week tirzepatide induced weight loss. Both groups will receive the same pharmacological equivalence treatment of tirzepatide throughout but only the intervention group (GLP-1+ EXC) will undertake the resistance exercise program. It is hypothesised that the intervention group will produce more favourable results and be classed as the superiority treatment.

Study Record Dates

• First Submitted: February 19, 2026
• First Posted: March 9, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: March 27, 2026

Record last verified: 2026-02

Locations

GB (1)