LEAN-PREP

RecruitingPhase NA

LEAN Mass Preservation With Resistance Exercise and Protein During Semaglutide/Tirzepatide Therapy

LEAN Mass Preservation With Resistance Exercise and Protein During Semaglutide and Tirzepatide Therapy (LEAN-PREP Study)

Lead sponsor

Dasman Diabetes Institute

Assets

Semaglutide / Tirzepatide

Listed sites

Recruiting sites

Enrollment

232

estimated

Study population

Obesity / overweight

Key I/E criterion

—

Primary endpoint

•MRI measured quadriceps cross sectional area (CSA)

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT06885736

Org study IDRA HM-2025-01

Timeline

Milestones

Study first posted2025-03-20actual

Study start2025-08-07actual

Last update posted2026-04-21actual

Primary completion2029-08-30estimated

Study completion2029-12-31estimated

Assets

Investigational agents

Semaglutide Tirzepatide

Study populations

Who this study enrolls

Obesity / overweight

Eligibility

Who can enroll

Minimum age18 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Age >/= 18 years

•BMI >/= 27 kg/m2

Exclusion criteria

•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

•Evidence of active autoimmune abnormality that is likely to requite systemic glucocorticoid treatment in the next 12 months

•Had or waiting for an organ transplant

•History of an active or untreated malignancy or in remission from a clinically significant malignancy for less than 5 years

•Any other aspect of history or condition that may limit the ability of the patient to complete the study

•Having been treated with prescription drugs that promote weight loss in the last 3 months

•Receiving chronic systemic glucocorticoid therapy within last month

Endpoints (24)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Weight & body composition

MASH / liver

Patient-reported / QoL

Other (unclassified)

Glycemic / diabetes

Cardiometabolic biomarkers

Other clinical outcomes

Heart failure

Renal / kidney

Safety / tolerability / PK

Weight & body composition

4 endpoints

Primary/protocol endpoint

MRI measured quadriceps cross sectional area (CSA)

Time frame:From enrollment (at baseline) to the end of treatment at 6 months.

change from baseline, improvement

Secondary/protocol endpoint

MRI measured intramuscular fat content (total thigh)

Time frame:From enrollment (at baseline) to the end of treatment at 6 months.

change from baseline, improvement

Secondary/protocol endpoint

Body Composition via DEXA scan

Time frame:From enrollment (at baseline) to the end of treatment at 6 months.

Total fat mass

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Muscle strength

Time frame:From enrollment (at baseline) to the end of treatment at 6 months.

change from baseline, improvement

Glycemic / diabetes

2 endpoints

Secondary/protocol endpoint

Whole blood glycated haemoglobin (HbA1c)

Time frame:From enrollment (at baseline) to the end of treatment at 6 months.

descriptive

LOINC 4548-4

Secondary/protocol endpoint

Oral glucose tolerance test

Time frame:From enrollment (at baseline) to the end of treatment at 6 months.

descriptive

MASH / liver

4 endpoints

Secondary/protocol endpoint

MRI measured liver fat

Time frame:From enrollment (at baseline) to the end of treatment at 6 months.

Liver fat content, change

change from baseline, improvement

Secondary/protocol endpoint

MRI measured liver stiffness

Time frame:From enrollment (at baseline) to the end of treatment at 6 months.

change from baseline, improvement

Secondary/protocol endpoint

Liver function

Time frame:From enrollment (at baseline) to the end of treatment at 6 months.

change from baseline, improvement

Secondary/protocol endpoint

Fibrosis-4 (FIB-4) Index Score

Time frame:From enrollment (at baseline) to the end of treatment at 6 months.

change from baseline, improvement

Heart failure

1 endpoint

Secondary/protocol endpoint

Aerobic Fitness

Time frame:From enrollment (at baseline) to the end of treatment at 6 months.

6-minute walk distance

change from baseline, improvement

Renal / kidney

1 endpoint

Secondary/protocol endpoint

eGFR

Time frame:From enrollment (at baseline) to the end of treatment at 6 months.

eGFR, change

change from baseline, improvement

LOINC 98979-8

Cardiometabolic biomarkers

2 endpoints

Secondary/protocol endpoint

Blood lipids profile

Time frame:From enrollment (at baseline) to the end of treatment at 6 months.

change from baseline, improvement

Secondary/protocol endpoint

hsCRP

Time frame:From enrollment (at baseline) to the end of treatment at 6 months.

hs-CRP, change

change from baseline, improvement

LOINC 30522-7

Patient-reported / QoL

4 endpoints

Secondary/protocol endpoint

Physical Activity Level

Time frame:From enrollment (at baseline) to the end of treatment at 6 months.

change from baseline, improvement

Secondary/protocol endpoint

Sleep Quality and Disturbances

Time frame:From enrollment (at baseline) to the end of treatment at 6 months.

change from baseline, improvement

Secondary/protocol endpoint

Health-Related Quality of Life

Time frame:From enrollment (at baseline) to the end of treatment at 6 months.

EQ-5D index

change from baseline, improvement

Secondary/protocol endpoint

Activities of Daily Living

Time frame:From enrollment (at baseline) to the end of treatment at 6 months.

change from baseline, improvement

Safety / tolerability / PK

1 endpoint

Secondary/protocol endpoint

Concomitant medication Use

Time frame:From enrollment (at baseline) to the end of treatment at 6 months.

descriptive

Other clinical outcomes

2 endpoints

Secondary/protocol endpoint

Chair rise performance

Time frame:From enrollment (at baseline) to the end of treatment at 6 months.

change from baseline, improvement

Secondary/protocol endpoint

Gait Speed

Time frame:From enrollment (at baseline) to the end of treatment at 6 months.

change from baseline, improvement

Other (unclassified)

3 endpoints

Secondary/protocol endpoint/low confidence

Inflammatory profiles

Time frame:From enrollment (at baseline) to the end of treatment at 6 months.

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Baseline Dietary intake

Time frame:Assessed at baseline (enrollment).

descriptive

Secondary/protocol endpoint/low confidence

Macronutrient Intake

Time frame:From enrollment (at baseline) to the end of treatment at 6 months.

descriptive

Publications (7)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

LEAN mass Preservation with Resistance Exercise and Protein during semaglutide and tirzepatide therapy (LEAN-PREP study): a protocol for a randomised controlled trial.
BMJ open2026 Apr 22PMID42020128doi:10.1136/bmjopen-2026-116911via clinicaltrials gov reference derived + pubmed nct search
The effect of home-based resistance exercise training in people with type 2 diabetes: A randomized controlled trial.
Diabetes/metabolism research and reviews2023 Oct (month)PMID37330638doi:10.1002/dmrr.3677via CT.gov background
Healthy Weight Loss Maintenance with Exercise, Liraglutide, or Both Combined.
The New England journal of medicine2021 May 6PMID33951361doi:10.1056/NEJMoa2028198via CT.gov background
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.
British journal of sports medicine2018 Mar (month)PMID28698222doi:10.1136/bjsports-2017-097608via CT.gov background
Resistance training is medicine: effects of strength training on health.
Current sports medicine reports2012 Jul-Aug (year)PMID22777332doi:10.1249/JSR.0b013e31825dabb8via CT.gov background
Physical activity advice only or structured exercise training and association with HbA1c levels in type 2 diabetes: a systematic review and meta-analysis.
JAMA2011 May 4PMID21540423doi:10.1001/jama.2011.576via CT.gov background
Increased protein intake reduces lean body mass loss during weight loss in athletes.
Medicine and science in sports and exercise2010 Feb (month)PMID19927027doi:10.1249/MSS.0b013e3181b2ef8evia CT.gov background

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 1, 2026

Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)

Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.