LEAN Mass Preservation With Resistance Exercise and Protein During Semaglutide/Tirzepatide Therapy
LEAN-PREP
1 other identifier
interventional
232
1 country
1
Brief Summary
The aim of the current study is to determine whether resistance exercise and/or protein intake can preserve lean mass and improve physical function in patients with obesity initiating semaglutide/tirzepatide therapy. To achieve this aim the study will have the following objectives. In people with obesity initiating semaglutide/tirzepatide therapy
- Control group
- Protein intake group
- Muscle strengthening exercise group
- Muscle strengthening exercise AND protein intake group.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable obesity
Started Aug 2025
Longer than P75 for not_applicable obesity
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 9, 2025
CompletedFirst Posted
Study publicly available on registry
March 20, 2025
CompletedStudy Start
First participant enrolled
August 7, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 30, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2029
April 21, 2026
April 1, 2026
4.1 years
March 9, 2025
April 19, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
MRI measured quadriceps cross sectional area (CSA)
At the mid-point of the thigh, investigators will measure the cross-sectional area of the quadriceps muscle and quantify muscle's thickness and size.
From enrollment (at baseline) to the end of treatment at 6 months.
Secondary Outcomes (23)
MRI measured intramuscular fat content (total thigh)
From enrollment (at baseline) to the end of treatment at 6 months.
MRI measured liver fat
From enrollment (at baseline) to the end of treatment at 6 months.
MRI measured liver stiffness
From enrollment (at baseline) to the end of treatment at 6 months.
Body Composition via DEXA scan
From enrollment (at baseline) to the end of treatment at 6 months.
Muscle strength
From enrollment (at baseline) to the end of treatment at 6 months.
- +18 more secondary outcomes
Study Arms (4)
Resistance exercise
EXPERIMENTALParticipants assigned to the resistance exercise group will be asked to perform exercises 3 times a week for the intervention period. The first 3 sessions of the exercise will be performed under the supervision of a qualified exercise specialist to ensure that the participants are happy with the exercises and are performing them appropriately. These will also be group sessions to encourage participants to build social connections to support them during the intervention. A similar group social session will take place at week 4 and then every 4 weeks of the study to overcome any issues with the exercises and to ensure progression to an appropriate intensity.
Protein Intake
EXPERIMENTALThe aim of this arm of the intervention is to ensure a protein intake of 1.6g/kg/day, as this was the intake level identified as the level after which no further effect was found on muscle mass in the meta-regression from (Morton et al., 2018). For the initial 2 weeks of the study, investigators will ask participants to consume 2 protein drinks, containing 25g protein (3g leucine), per day - one in the morning and one in the evening. At this stage, investigators won't know the magnitude of reduction of protein intake following initiation of semaglutide/tirzepatide treatment. After 2 weeks, when the first assessment of dietary intake after beginning semaglutide/tirzepatide treatment occurs, the additional protein will be based on the amount required to ensure 1.6g/kg/day with an aim to spread protein evenly across the day and aim for at least 25g protein (3g leucine) per meal or snack.
Resistance exercise + protein intake
EXPERIMENTALParticipants in this arm will follow the above resistance exercise and protein intake interventions.
Control
NO INTERVENTIONParticipants assigned to the control group will be asked to maintain their usual exercise habits
Interventions
Participants assigned to the resistance exercise group will be asked to perform exercises 3 times a week for the intervention period. The first 3 sessions of the exercise will be performed under the supervision of a qualified exercise specialist to ensure that the participants are happy with the exercises and are performing them appropriately. These will also be group sessions to encourage participants to build social connections to support them during the intervention. A similar group social session will take place at week 4 and then every 4 weeks of the study to overcome any issues with the exercises and to ensure progression to an appropriate intensity.
The aim of this arm of the intervention is to ensure a protein intake of 1.6g/kg/day, as this was the intake level identified as the level after which no further effect was found on muscle mass in the meta-regression from (Morton et al., 2018). For the initial 2 weeks of the study, investigators will ask participants to consume 2 protein drinks, containing 25g protein (3g leucine), per day - one in the morning and one in the evening. At this stage, investigators won't know the magnitude of reduction of protein intake following initiation of semaglutide/tirzepatide treatment. After 2 weeks, when the first assessment of dietary intake after beginning semaglutide/tirzepatide treatment occurs, the additional protein will be based on the amount required to ensure 1.6g/kg/day with an aim to spread protein evenly across the day and aim for at least 25g protein (3g leucine) per meal or snack.
Eligibility Criteria
You may qualify if:
- Age \>/= 18 years
- BMI \>/= 27 kg/m2
You may not qualify if:
- Currently or in the past 6 months participating in any vigorous aerobic activity (\>1h per week) or any resistance exercise.
- BP of 160/100mmHg or higher
- Any known medical condition that prevents participants from exercising safely
- A personal or family history of medullary thyroid carcinoma
- Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
- History of chronic or acute pancreatitis
- History of proliferative diabetic retinopathy or diabetic maculopathy
- History of ketoacidosis or hyperosmolar state/coma
- History of severe hypoglycaemia and/or hypoglycaemia unawareness within last 6 months
- Clinically significant gastric emptying abnormality or have undergone or plan to undergo gastric bypass or restrictive bariatric surgery or chronically taking drugs that directly affect GI motility
- Any of the following CV conditions in last 2 months: acute MI, stroke or hospitilisation due to CHF
- History of NYHA IV CHF
- Acute or chronic hepatitits, signs and symptoms of any liver disease other than NAFLD, ALT \> 3 times the upper limit of normal
- eGFR \<45mL/min/1.73m2
- Significant uncontrolled endocrine abnormaility in the opinion of clinical investigator
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Dasman Diabetes Institutelead
- University of Glasgowcollaborator
Study Sites (1)
Dasman Diabetes Institute
Kuwait City, Kuwait
Related Publications (6)
Morton RW, Murphy KT, McKellar SR, Schoenfeld BJ, Henselmans M, Helms E, Aragon AA, Devries MC, Banfield L, Krieger JW, Phillips SM. A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults. Br J Sports Med. 2018 Mar;52(6):376-384. doi: 10.1136/bjsports-2017-097608. Epub 2017 Jul 11.
PMID: 28698222BACKGROUNDMettler S, Mitchell N, Tipton KD. Increased protein intake reduces lean body mass loss during weight loss in athletes. Med Sci Sports Exerc. 2010 Feb;42(2):326-37. doi: 10.1249/MSS.0b013e3181b2ef8e.
PMID: 19927027BACKGROUNDLundgren JR, Janus C, Jensen SBK, Juhl CR, Olsen LM, Christensen RM, Svane MS, Bandholm T, Bojsen-Moller KN, Blond MB, Jensen JB, Stallknecht BM, Holst JJ, Madsbad S, Torekov SS. Healthy Weight Loss Maintenance with Exercise, Liraglutide, or Both Combined. N Engl J Med. 2021 May 6;384(18):1719-1730. doi: 10.1056/NEJMoa2028198.
PMID: 33951361BACKGROUNDWestcott WL. Resistance training is medicine: effects of strength training on health. Curr Sports Med Rep. 2012 Jul-Aug;11(4):209-16. doi: 10.1249/JSR.0b013e31825dabb8.
PMID: 22777332BACKGROUNDUmpierre D, Ribeiro PA, Kramer CK, Leitao CB, Zucatti AT, Azevedo MJ, Gross JL, Ribeiro JP, Schaan BD. Physical activity advice only or structured exercise training and association with HbA1c levels in type 2 diabetes: a systematic review and meta-analysis. JAMA. 2011 May 4;305(17):1790-9. doi: 10.1001/jama.2011.576.
PMID: 21540423BACKGROUNDAl Ozairi E, Alsaeed D, Al Roudhan D, Jalali M, Mashankar A, Taliping D, Abdulla A, Gill JMR, Sattar N, Welsh P, Gray SR. The effect of home-based resistance exercise training in people with type 2 diabetes: A randomized controlled trial. Diabetes Metab Res Rev. 2023 Oct;39(7):e3677. doi: 10.1002/dmrr.3677. Epub 2023 Jun 17.
PMID: 37330638BACKGROUND
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Masking Details
- The researcher and the participant will be blinded to the allocation pattern. It is not possible to blind participants to treatment allocation but people making outcome measurements and performing statistical analysis will be blinded.
- Purpose
- BASIC SCIENCE
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Chief Medical Officer (CMO)
Study Record Dates
First Submitted
March 9, 2025
First Posted
March 20, 2025
Study Start
August 7, 2025
Primary Completion (Estimated)
August 30, 2029
Study Completion (Estimated)
December 31, 2029
Last Updated
April 21, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- The data will remain available for 5 years following publication
The individual participant data (IPD) that underlie the results reported in this study, along with the study protocol and statistical analysis plan, will be made available upon reasonable request. Requests should be directed to the corresponding author and will be subject to review to ensure compliance with legal, ethical, and confidentiality requirements.