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April 24, 2026BMJ Open4 citationsOpen Access

LEAN mass Preservation with Resistance Exercise and Protein during semaglutide and tirzepatide therapy (LEAN-PREP study): a protocol for a randomised controlled trial

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AAAmeenah A AlawadhiDADherar AlroudhanDADalal J Alsaeed

Key Points

  • This trial aims to assess whether resistance exercise and protein supplementation can mitigate muscle mass loss during GLP-1 therapy.
  • Randomised controlled trial design with four groups: control, resistance exercise, protein supplementation, and combined intervention.
  • Home-based resistance exercise targeting major muscle groups, progressing from one to three sets, three times per week.
  • Assessments include MRI for quadriceps area and liver fat, along with body composition, strength, physical function, and metabolic markers.
  • Primary outcome: change in quadriceps cross-sectional area as measured by MRI.
  • Secondary outcomes include improvements in body composition and physical function.
  • Study expected to provide insights into preserving lean mass while losing weight during GLP-1 therapy.

Abstract

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 .

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Cite This Study

Alawadhi et al. (2026) studied this question.

synapsesocial.com/papers/69eb0a66553a5433e34b486fhttps://doi.org/10.1136/bmjopen-2026-116911
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