Preserving musculoskeletal health through resistance training in individuals undergoing Glucagon-like Peptide-1 Receptor Agonist Therapy: a controlled interrupted time-series analysis (Stage 1 Registered Report)

Abstract Glucagon-like peptide-1 receptor agonists (GLP-1-RAs) are increasingly prescribed for weight loss and cardiometabolic health but have been evidenced to lead to loss of lean soft tissue mass. Resistance training (RT) is known to result in increase muscle mass, and indeed preserve muscle mass during weight loss through more traditional weight loss approaches such as energy restriction and bariatric surgery. Yet, its effectiveness in counteracting GLP-1-RA–associated lean soft tissue mass loss remains unclear. This Stage 1 Registered Report outlines a quasi-experimental, retrospective, controlled interrupted time-series analysis using existing data from Kieser Australia members undergoing standardized RT intervention. Participants identified by internal survey to have also been on, or are currently on, GLP-1-RA therapy will be propensity score–matched to controls not receiving the drug. The primary outcome is fat free mass (via bioelectrical impedance analysis), serving as a proxy for lean soft tissue mass. We hypothesize that the effect of RT over time will be non-inferior to the effect of GLP-1-RA, indicating mitigation of lean mass loss. Secondary exploratory outcomes include effects on muscle strength. Simulations regarding estimates of GLP-1-RA treatment use in the Kieser Australia membership suggest we will be able to obtain a sample size of 37 [interquartile range: 8] matched participants per group and that, using additive estimates of the effects of RT and GLP-1-RA treatments from prior meta-analyses suggest adequate we will achieved at least 80% power at an alpha of 0.05 for testing non-inferiority with this sample size. Results will inform clinical strategies to preserve musculoskeletal health during pharmacological weight loss interventions. Competing Interest Statement JS, MNM, and PM at the time of writing are employed by Kieser Australia. JS is also a recommender for Peer Community In Registered Reports (where this manuscript is under review). Funding Statement No direct funding has been received for the present study. All costs are internally absorbed by Kieser Australia. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This project is deemed to fall under the exemption from a priori review and approval under the Australian NHMRC National Statement on Ethical Conduct in Human Research 2023, in addition to other guidelines such as those of the UK Research Integrity Office, as it considered to be low risk. The project will involve use of existing data only in deidentified form that is collected from Kieser Australia members with full informed consent already captured for research use as standard part of members contracts. The only additional prospective data capture will be the brief internal survey to members aiding us in identifying those from our membership who meet the characteristics for the intervention group; in this case, those who respond to self-report and identify themselves as having been on, or are currently undergoing, GLP-1-RA treatment. Internal member surveys are commonly conducted by Kieser Australia and do not require any a priori ethical approval under any existing legislative or guidance documentation that Kieser Australia is subject to. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Footnotes We have corrected two typos that were in the abstract. Data Availability All materials, code, and deidentified data are/will be available on the Github repository for this project (https://github.com/jamessteeleii/glp1_rt_cits) and linked to the corresponding Open Science Framework project page (https://osf.io/r4s9b/).