Muscle Mass and StrengthFLEXNCT07457437
Function and Lean Mass Preservation With Resistance Exercise During a GLP-1RA Treatment
A study testing Progressive Resistance Exercise Training Program and Habitual physical activity guidelines in people with Muscle Mass and Strength and Obesity & Overweight, run by University of Exeter at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 25 to 50 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Muscle Mass and Strength, Obesity & Overweight, Physical Function
- What is being tested?
- Progressive Resistance Exercise Training Program and Habitual physical activity guidelines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Apr 2026to 1 Dec 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 50 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 25-50 years old
- BMI ≥27 kg/m2 with one obesity related co-morbidity or a BMI between ≥30 and 35 kg/m2
- Female
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom1 site, 1 recruiting
- Recruiting
Nutritional Physiology Research Unit
Exeter, Devon, EX2 4TH
Professor Francis Stephens, 01392 6612157, F.B.Stephens@exeter.ac.uk
Professor Benjamin Wall, 01392 72 4774, B.T.Wall@exeter.ac.uk
About this study
Official title: Effect of a Progressive Resistance Exercise Program on Muscle Mass and Physical Function During a Tirzepatide Induced Weight Loss in Overweight and Obese Females: a Randomised Parallel Group Study
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.
Read the detailed description
Glucagon-like peptide-1 receptor agonists (GLP-1RA's) are an emerging efficient class of anti-obesity medicines. With the constant development of new weight loss pharmacotherapies substantial body mass losses (~21%) have been observed with dual receptor agonist [GLP-1/GIP (glucose-dependent insulinotropic polypeptide)] drugs such as tirzepatide. Whilst the weight losses are promising for those living with overweight or obesity, one concern with these medications is the large lean mass losses associated with them. With previous reviews stating 20-50% of GLP-1RA weight loss is from lean mass losses and more recently 15mg of tirzepatide weekly was shown to cause an 11% reduction in lean mass over 72 weeks. This is a big concern as once discontinued, weight regain after GLP-1 use can be as extreme as 15% of body mass in a year. Placing patients at a risk of sarcopenic obesity in the future with reduced skeletal muscle mass and potentially higher fat to muscle ratio's than before treatment, putting them at greater risk of reduced mobility, diabetes and other serious health conditions. Resistance training has been shown to maintain and even improve lean mass amounts during less severe weight loss periods in obese individuals. Previously this research group has shown that a 12-week low impact resistance band training program was effective in increasing muscle mass and function in pre, peri, and post-menopausal females. Therefore, this study aims to determine if progressive resistance exercise training can mitigate or reverse the large lean mass losses seen with GLP-1/GIP treatment in females.
Sixty overweight or obese females age 25-50 with a BMI ≥27kg/ m2 with one obesity related comorbidity or a BMI between ≥ 30 to 35kg/m2 will be randomised into two groups. The GLP-1 Group (GLP-1) will be given a standard prescription of tirzepatide as per the manufacturer and NICE guidelines for 20 weeks. 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. The primary outcome of skeletal muscle mass will be determined by ultrasound and the D3-Creatine isotope tracer method which both measure muscle mass directly rather than lean mass or lean soft tissue. Secondary outcomes of strength and physical function will be measured by knee extensor and elbow flexor isokinetic dynamometry, 60sec sit to stand test (STS60), hand grip strength and Y Balance Test. Body composition, dietary intake, gastrointestinal (GI) distress, quality of life, and sleep score, will be measured by Bioelectrical Impedance (BIA), app-based food diary taken 3 days a week (2 weekdays and 1 weekend), questionnaires and accelerometers. Body mass will be measured daily by the participants and on every laboratory visit. Testing will take place at baseline and then weekly, 4th weekly, mid and post. Please see Figures 1 and 2 below for the testing schedule. A subset (n=24) of participants will undergo voluntary muscle biopsies in order to provide insight into mechanisms of any differences in muscle mass between groups.
Participants will be invited back for follow up testing at 40 weeks and 72 weeks (Figure 3) to repeat the above measures to provide insight into any weight regain and body composition changes once participants have stopped GLP-1/GIP treatment.
This study will provide new data of actual muscle mass preservation while taking GLP-1RA drugs alongside the amount of muscle mass preservation a progressive resistance exercise program can provide while taking GLP-1RA drugs. Previous work around body composition changes whilst using GLP-1RA's has only utilised lean and fat free mass values to quantify muscle mass. Our measures of ultrasound and D-3 Creatine will give more valid, direct measures of skeletal muscle. Comparison in any changes between groups could further provide insight into the advantages of participating in resistance exercise during GLP-1-RA treatment after cessation of GLP-1RA treatment.
- Being tested
- Progressive Resistance Exercise Training Program, Habitual physical activity guidelines
- 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
- Medical subject headings
- Obesity, Overweight
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Progressive Resistance Exercise Training ProgramOther
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.
Habitual physical activity guidelinesOther
Control group consisting of continuing habitual physical activity guidelines for 20 weeks
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: Progressive Resistance Exercise Training Program |
| GLP-1RA | Placebo comparator | Habitual physical activity guidelines Receives: Other: Habitual physical activity guidelines |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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)
Knee extension and elbow flexion peak torque (PT) will be measured by an isokinetic dynamometer (Biodex Medical Systems, Shirley, NY). Participants will be positioned according to the Biodex manual (Biodex Medical Systems 3) at the familiarization visit and all subsequent visits. Before the test participants will warm up for 5 mins at 60-90rpm on a stationary bike (Watt Bike Atom; Wattbike Ltd, Nottingham, UK) and perform three repetitions on the dynamometer at 30, 60 and 90% effort. Participants will then perform 2 x 5 repetitions of maximal isokinetic contractions separated by 90s rest, the highest value will be taken as PT. Verbal encouragement will l be provided by the researcher during each test.
Measured: 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 (%)
Knee extension and elbow flexion fatigue profile will then be measured on the isokinetic dynamometer (Biodex Medical Systems, Shirley, NY) after 3 minutes rest. Participants will perform 30 maximal-effort concentric repetitions on their dominant limbs.
Measured: 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
One minute Sit to Stand test (1MSTST) participants will be asked to stand up and sit down as many times as possible in 60 seconds on to a conventional chair without arm rests. The number of completed repetitions in 60 seconds will be recorded.
Measured: 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
Dynamic balance will be measured using the Y-balance test (LQ-YBT). Participants will be asked to move a reach indicator block as far as possible in the anterior (ANT), posteromedial (PM), and posterolateral (PL) directions with their non standing foot from the central block of the YBT Kit TM (Fysio Supplies B.V). Participant hands will stay on hips and the heel will remain flat. Distances will be measured to the nearest half centimetre.
Measured: 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
Hand grip strength will be measured on each hand alternatively using the handgrip dynamometer (Takei, JAPAN) standing with arms parallel to the trunk. Three maximal attempts will be performed on each arm.
Measured: 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
Body Mass (kg)
Body mass will be reported weekly with scales provided for the participants remotely and will be measured via BIA scales in the NPRU lab on each visit.
Measured: Body mass will be taken weekly and reported to the researchers by participants for weeks 0-20. It will then also be taken at the follow up visits at weeks 40 and 72.
Height (cm)
Height will be measured in centimetres at the baseline visit.
Measured: The measure will be taken at the commencement of the study at week 0 during the baseline visit.
Body Composition
Fat Mass and Lean Mass will be measured via BIA in the NPRU lab.
Measured: Fat and lean mass will also be measure every 4 weeks and also be measure at two separate time points during a follow up study at week 40 and 72 weeks from week 0.
Plasma Tirzepatide
Plasma Tirzepatide will be measure retrospectively via LCMS
Measured: Blood samples will be taken at weeks 0,4,8,10,12,16 and 20.
Hba1c
Whole blood Hba1c will be measured via venepuncture blood sample.
Measured: Blood samples will be taken at weeks 0,4,8,10,12,16 and 20 as well as the follow up visits at weeks 40 and 72
Estradiol-β17
Serum estradiol-β17 will be analysed from baseline blood samples.
Measured: Serum estradiol-β17 will be measured at baseline (week 0)
Progesterone
Serum progesterone will be analysed from baseline blood samples.
Measured: Serum progesterone will be measured at baseline (Week 0)
Gastrointestinal Symptom Rating Scale Questionnaire (GSRS)
The GSRS will be completed remotely from week 0-20 to assess GI symptoms and act as a monitoring tool of participants. Each question is scored from 1-7 with 1 showing no discomfort at all and 7 showing very severe discomfort. The scores to the 15 questions provide an overall score between 15-105 as well as grouped scores for different categories which are: reflux, abdominal pain, indigestion, diarrhoea and constipation.
Measured: The GSRS will be completed remotely from week 0-20 to assess GI symptoms and act as a monitoring tool of participants
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2026
- Study start1 Apr 2026 (estimated)
- Primary completion1 Dec 2027 (estimated)
- Study completion1 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Muscle Mass and StrengthStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Exeter
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Francis Stephens, University of Exeter
- Investigators
- Francis B Stephens, PhD, Principal investigator, University of Exeter
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07457437
- Sponsor's protocol ID
- 11468874
- Acronym
- FLEX
- Status last verified
- Feb 2026
- First submitted
- 19 Feb 2026
- Last updated
- 27 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: At present there is no plan to share IPD, however this may change due to the magnitude of individuals data or the request of researchers. Any individual participant data that is shared will be anonymised. IPD will be collected throughout the study and will be collated into password protected spreadsheets and stored under a link anonymised study ID. Data for the two experimental groups will then be used to generate group means which will be statistically analysed. At present only group mean and standard deviation data will shared and published.
Publications
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.
PubMed 39480197Verreijen 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.
PubMed 28166780Look 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.
PubMed 39996356Sargeant 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.
PubMed 31565876Jastreboff 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.
PubMed 35658024
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of a Progressive Resistance Exercise Program on Muscle Mass and Physical Function During a Tirzepatide Induced Weight Loss in Overweight and Obese Females: a Randomised Parallel Group Study
- ClinicalTrials.gov ID
- NCT07457437
- Acronym / sponsor ID
- FLEX / 11468874
- 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
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- University of ExeterUniversity, hospital or other
- Study start
- 1 Apr 2026 (estimated)
- Primary completion
- 1 Dec 2027 (estimated)
- Study completion
- 1 Dec 2027 (estimated)
- First posted
- 9 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Glucagon-like peptide-1 receptor agonists (GLP-1RA's) are an emerging efficient class of anti-obesity medicines. With the constant development of new weight loss pharmacotherapies substantial body mass losses (~21%) have been observed with dual receptor agonist [GLP-1/GIP (glucose-dependent insulinotropic polypeptide)] drugs such as tirzepatide. Whilst the weight losses are promising for those living with overweight or obesity, one concern with these medications is the large lean mass losses associated with them. With previous reviews stating 20-50% of GLP-1RA weight loss is from lean mass losses and more recently 15mg of tirzepatide weekly was shown to cause an 11% reduction in lean mass over 72 weeks. This is a big concern as once discontinued, weight regain after GLP-1 use can be as extreme as 15% of body mass in a year. Placing patients at a risk of sarcopenic obesity in the future with reduced skeletal muscle mass and potentially higher fat to muscle ratio's than before treatment, putting them at greater risk of reduced mobility, diabetes and other serious health conditions. Resistance training has been shown to maintain and even improve lean mass amounts during less severe weight loss periods in obese individuals. Previously this research group has shown that a 12-week low impact resistance band training program was effective in increasing muscle mass and function in pre, peri, and post-menopausal females. Therefore, this study aims to determine if progressive resistance exercise training can mitigate or reverse the large lean mass losses seen with GLP-1/GIP treatment in females.
Sixty overweight or obese females age 25-50 with a BMI ≥27kg/ m2 with one obesity related comorbidity or a BMI between ≥ 30 to 35kg/m2 will be randomised into two groups. The GLP-1 Group (GLP-1) will be given a standard prescription of tirzepatide as per the manufacturer and NICE guidelines for 20 weeks. 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. The primary outcome of skeletal muscle mass will be determined by ultrasound and the D3-Creatine isotope tracer method which both measure muscle mass directly rather than lean mass or lean soft tissue. Secondary outcomes of strength and physical function will be measured by knee extensor and elbow flexor isokinetic dynamometry, 60sec sit to stand test (STS60), hand grip strength and Y Balance Test. Body composition, dietary intake, gastrointestinal (GI) distress, quality of life, and sleep score, will be measured by Bioelectrical Impedance (BIA), app-based food diary taken 3 days a week (2 weekdays and 1 weekend), questionnaires and accelerometers. Body mass will be measured daily by the participants and on every laboratory visit. Testing will take place at baseline and then weekly, 4th weekly, mid and post. Please see Figures 1 and 2 below for the testing schedule. A subset (n=24) of participants will undergo voluntary muscle biopsies in order to provide insight into mechanisms of any differences in muscle mass between groups.
Participants will be invited back for follow up testing at 40 weeks and 72 weeks (Figure 3) to repeat the above measures to provide insight into any weight regain and body composition changes once participants have stopped GLP-1/GIP treatment.
This study will provide new data of actual muscle mass preservation while taking GLP-1RA drugs alongside the amount of muscle mass preservation a progressive resistance exercise program can provide while taking GLP-1RA drugs. Previous work around body composition changes whilst using GLP-1RA's has only utilised lean and fat free mass values to quantify muscle mass. Our measures of ultrasound and D-3 Creatine will give more valid, direct measures of skeletal muscle. Comparison in any changes between groups could further provide insight into the advantages of participating in resistance exercise during GLP-1-RA treatment after cessation of GLP-1RA treatment.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| GLP-1RA+EXERCISE | Experimental | Other: Progressive Resistance Exercise Training ProgramIn 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. |
| GLP-1RA | Placebo comparator | Other: Habitual physical activity guidelinesHabitual physical activity guidelines |
Who may qualify
- Ages
- 25 to 50 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 25-50 years old
- BMI ≥27 kg/m2 with one obesity related co-morbidity or a BMI between ≥30 and 35 kg/m2
- Female
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Progressive Resistance Exercise Training ProgramParticipants 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. | Other | GLP-1RA+EXERCISE |
| Habitual physical activity guidelinesControl group consisting of continuing habitual physical activity guidelines for 20 weeks | Other | GLP-1RA |
Primary outcome
Skeletal Muscle Mass
Time frame: 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 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.
Muscle Thickness (Ultrasound)
Time frame: 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.
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.
13 secondary outcomes
Isokinetic dynamometry (Bicep and Quadriceps) Peak Torque (Nm/kg)
Time frame: 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 (%)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Body Mass (kg)
Time frame: Body mass will be taken weekly and reported to the researchers by participants for weeks 0-20. It will then also be taken at the follow up visits at weeks 40 and 72.
Height (cm)
Time frame: The measure will be taken at the commencement of the study at week 0 during the baseline visit.
Body Composition
Time frame: Fat and lean mass will also be measure every 4 weeks and also be measure at two separate time points during a follow up study at week 40 and 72 weeks from week 0.
Plasma Tirzepatide
Time frame: Blood samples will be taken at weeks 0,4,8,10,12,16 and 20.
Hba1c
Time frame: Blood samples will be taken at weeks 0,4,8,10,12,16 and 20 as well as the follow up visits at weeks 40 and 72
Estradiol-β17
Time frame: Serum estradiol-β17 will be measured at baseline (week 0)
Progesterone
Time frame: Serum progesterone will be measured at baseline (Week 0)
Gastrointestinal Symptom Rating Scale Questionnaire (GSRS)
Time frame: The GSRS will be completed remotely from week 0-20 to assess GI symptoms and act as a monitoring tool of participants
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2026.
- Background: PubMed 39480197Svensen 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.
- Background: PubMed 28166780Verreijen 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.
- Background: PubMed 39996356Look 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.
- Background: PubMed 31565876Sargeant 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.
- Background: PubMed 35658024Jastreboff 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.
- Individual participant dataSharing planned: Undecided. At present there is no plan to share IPD, however this may change due to the magnitude of individuals data or the request of researchers. Any individual participant data that is shared will be anonymised. IPD will be collected throughout the study and will be collated into password protected spreadsheets and stored under a link anonymised study ID. Data for the two experimental groups will then be used to generate group means which will be statistically analysed. At present only group mean and standard deviation data will shared and published.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Francis B Stephens, PhD principal investigator
University of Exeter
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Progressive Resistance Exercise Training Program and Habitual physical activity guidelines in people with Muscle Mass and Strength and Obesity & Overweight, run by University of Exeter at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Thomas P J Kennedy, MSc (+44 7470074405, tk509@exeter.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Skeletal Muscle Mass (time frame: 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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07457437, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2026.