LEAN mass Preservation with Resistance Exercise and Protein during semaglutide and tirzepatide therapy (LEAN-PREP study): a protocol for a randomised controlled trial.
Semaglutide and tirzepatide aren't just buzzwords — they're two of the most discussed research peptides in the world of metabolic health. The LEAN-PREP study, launching out of Kuwait, is about to dig into a question that’s been on every researcher’s mind: How do you keep muscle while dropping weight with these compounds?
BMJ Open
by Alawadhi AA, Alroudhan D, Alsaeed DJ et al.
“LEAN mass Preservation with Resistance Exercise and Protein during semaglutide and tirzepatide therapy (LEAN-PREP study): a protocol for a randomised controlled trial. Alawadhi AA(1), Alroudhan D(2), Alsaeed DJ(1), Almarshad BW(1), Alshehabi DH(1), Allahou BA(3), Mashankar A(4), Al Ozairi E(5), Gray S(6). Author information: (1)Clinical Care Research and Trials, Dasman Diabetes Institute, Kuwait City, Kuwait. (2)Education and Training Unit, Dasman Diabetes Institute, Kuwait City, Kuwait. (3)Nutrition Unit, Dasman Diabetes Institute, Kuwait City, Kuwait. (4)Medical Division, Dasman Diabetes Institute, Kuwait City, Kuwait. (5)Medical Division, Dasman Diabetes Institute, Kuwait City, Kuwait ebaa.alozairi@dasmaninstitute.org. (6)Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK. INTRODUCTION: Obesity is a global public health issue, with its effects a particular issue in Kuwait. Advances in pharmaceutical treatment (eg, glucagon-like peptide-1s) offer an effective solution, with the magnitude of weight lost something to celebrate. However, this level of weight loss also results in dramatic reductions in lean mass, reflecting loss of muscle mass and muscle strength which can predispose people to sarcopenia. This is a particular issue in people with type 2 diabetes in Kuwait, where the prevalence of muscle weakness is extremely high. Solutions to mitigate this loss of muscle mass and strength are needed, with a pragmatic resistance exercise intervention and increasing dietary protein intake having potential. This trial aims to determine whether resistance exercise and/or protein intake can preserve muscle mass and improve physical function in people with obesity initiating semaglutide/tirzepatide therapy. METHODS AND ANALYSIS: This single-centre, 6-month, randomised controlled trial at Dasman Diabetes Institute will enrol 232 adults with obesity, randomised (1:1:1:1) to control, resistance exercise, protein supplementation or combined resistance exercise and protein in conjunction with semaglutide or tirzepatide therapy. Resistance exercise will be home-based and involve three sessions per week, progressing from one to three sets targeting major muscle groups. Protein supplementation will target 1.6 g/kg/day via dietary adjustment and protein products. Assessments at baseline and 6 months will include MRI measured quadriceps cross-sectional area (primary outcome), plus measures of secondary outcomes of MRI measured liver fat content and stiffness and intramuscular fat, body composition (dual energy X-ray absorptiometry), strength, physical function, dietary assessment, physical activity levels, sleep patterns, quality of life, glycaemic control and metabolic biomarkers. ETHICS AND DISSEMINATION: The study has received ethical approval from the Dasman Diabetes Institute Ethical Review Committee (HR-RA-2025-01, 19 February 2025) and is registered at ClinicalTrials.gov (NCT06885736, 26 June 2025). Written informed consent will be obtained from all participants, with no financial compensation provided. Data will be reported in accordance with Consolidated Standards of Reporting Trials (CONSORT) guidelines, ensuring participant anonymity. Findings will be disseminated through peer-reviewed publications and presentations at national and international conferences. TRIAL REGISTRATION NUMBER: NCT06885736. © Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. Conflict of interest statement: Competing interests: None declared.”
Here’s the deal. People using semaglutide or tirzepatide see major fat loss. But with that, lean mass — including muscle — often gets caught in the crossfire. That’s not ideal, especially in populations already dealing with muscle weakness, like those with type 2 diabetes in Kuwait.
The LEAN-PREP trial is running a six-month, randomized controlled setup with 232 adults. Four groups: standard care, resistance exercise, protein supplementation, and a combo of both — all while on either semaglutide or tirzepatide. The goal is simple: Find out if extra protein and resistance training can protect muscle size and function.
Key details:
Resistance training is home-based, three times a week, scaling up in intensity.
Protein supplementation targets 1.6g per kg per day, using diet tweaks and protein products.
Primary outcome: MRI scans of quadriceps muscle size — a direct measure of lean mass.
Secondary outcomes include liver fat, body composition (via DEXA), strength, metabolic markers, and more.
This study is tightly controlled and follows top-tier research standards. No one’s getting paid to show up, and results will get pushed out to journals and conferences — not locked in a drawer.
For researchers interested in sourcing quality compounds, check our vendor directory for reliable options.
Bottom line: The LEAN-PREP study could finally show how to keep muscle gains in the peptide era. Watch this space.
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