Determination of Resistance Training Status for Patients on Glucagon-Like Peptide-1 Receptor Agonists

Background and Rationale Glucagon-like peptide-1 (GLP-1) is a naturally occurring hormone released from enteroendocrine cells after a meal. It slows gastric emptying, limits maximum nutrient absorption, and helps prevent weight gain. GLP-1's actions also include preventing beta-cell death, promoting beta-cell proliferation, and regulating glucose metabolism. Originally used to improve outcomes in people with type 2 diabetes, GLP-1 receptor agonists (GLP-1RAs) have increasingly been prescribed for chronic weight management in individuals with overweight or obesity, with agents such as liraglutide 3 mg and semaglutide 2.4 mg approved for people with a body mass index of at least 30 kg/m2, or 27 kg/m2 with weight-related comorbidities. From 2019 to 2023, use of GLP-1RAs for weight loss in the United States rose from approximately 21,000 to 174,000 users, an increase of more than 700%.

A recognized side effect of GLP-1RA therapy is a reduction in lean tissue mass. Losses in lean mass can impair quality of life and physical function by decreasing strength, slowing gait speed, and increasing fatigue. Reductions in muscle mass may also heighten fall risk, worsen metabolic health, and limit patients' ability to perform activities of daily living independently.

Resistance training (RT) is the most effective strategy for preserving and building muscle mass and strength. The American College of Sports Medicine (ACSM) recommends that adults engage in RT at least 2-3 times per week at moderate to vigorous intensity, focusing on all major muscle groups. However, national surveillance data indicate that only about 30% of U.S. adults meet the muscle-strengthening guidelines. Despite emerging evidence that combining GLP-1RAs with structured exercise - particularly RT - can mitigate lean mass loss and optimize long-term metabolic and functional outcomes, little is known about patients' RT behavior before and after initiating GLP-1RA therapy.

This study aims to systematically collect self-reported data from adults using GLP-1RAs on their RT participation and adherence to ACSM-aligned guidelines before and after starting the medication, in order to identify gaps in RT engagement and generate practical recommendations for researchers and practitioners seeking to prevent lean mass loss, preserve physical function, and improve quality of life in this growing patient population.

Specific Aims and Hypotheses Aim 1: Quantify the prevalence of resistance training participation among adults using GLP-1RAs, both before and after initiating GLP-1RA therapy.

• Hypothesis 1a: A minority of GLP-1RA users meet ACSM muscle-strengthening guidelines prior to starting the medication.
• Hypothesis 1b: RT participation and adherence do not increase after GLP-1RA initiation and may decline in some patients.

Aim 2: Characterize patterns of RT dosage (frequency, intensity, type, and volume) in GLP-1RA users and compare them to ACSM-aligned recommendations.

• Hypothesis 2: Most GLP-1RA users who report RT perform it at a frequency and intensity below ACSM guidelines for optimal lean mass preservation.

Aim 3: Explore associations between RT participation and self-reported outcomes related to lean mass preservation, physical function, and quality of life in GLP-1RA users.

• Hypothesis 3: GLP-1RA users who meet RT guidelines report better perceived strength, functional capacity (e.g., ability to perform daily tasks), and health-related quality of life than those who do not perform RT.

Aim 4: Identify patient-reported barriers and facilitators to engaging in RT while using GLP-1RAs, to inform future intervention development.

• Hypothesis 4: Common barriers will include lack of knowledge about RT benefits during GLP-1RA therapy, limited access to equipment or programs, and fear of injury.

Study Design This is a cross-sectional, anonymous, online survey study. Adults currently using GLP-1RAs will complete a single online questionnaire assessing RT participation before and after starting GLP-1RA therapy, RT dosage patterns, perceived functional and quality-of-life outcomes, and perceived barriers and facilitators to RT. There are no in-person visits, no interventions, and no biological specimen collection. All data are self-reported in one online session lasting approximately 10 minutes.

Recruitment Potential participants will be identified through multiple channels, including: flyers and posters placed in relevant clinical settings (e.g., endocrinology, primary care); social media outreach (e.g., posts or advertisements targeting adults using GLP-1RAs); and clinic-based outreach in which the study team provides IRB-approved recruitment flyers and study links to participating clinic staff (e.g., front desk staff, providers, care coordinators) for posting in clinic waiting areas or distribution to potentially interested patients during routine visits. The study team will not pre-screen or identify patients via medical records, and clinic staff will not share any patient identifiers with the study team. Interested patients will self-refer by accessing the survey link from the flyer or handout. The study team will not access, request, or use any medical records or protected health information (PHI) for recruitment, screening, enrollment, or analysis.

Procedures The full participant workflow is as follows: (1) potential participants encounter an IRB-approved recruitment flyer, poster, social media post/advertisement, or clinic-distributed handout describing the study and listing a secure survey URL and/or QR code; (2) interested individuals self-initiate contact by clicking the link or scanning the QR code on a device of their choice, at a time and place of their choosing; (3) the link directs them to the electronic informed consent page on the institution-approved survey platform (Qualtrics) hosted on Ohio State University secure servers; (4) individuals who indicate willingness to participate by selecting "I agree to participate" proceed to brief eligibility screening; (5) individuals who meet all inclusion and no exclusion criteria proceed automatically to the main questionnaire, while ineligible individuals are routed to a thank-you/exit message; (6) eligible participants complete the one-time questionnaire and exit the platform.

The main questionnaire assesses: demographic and general health information; current height and weight and weight at the time of GLP-1RA initiation; specific GLP-1RA medication, indication, start date, starting dose, and current dose; resistance training habits in a usual week before starting the GLP-1RA medication; resistance training habits in a usual week since starting the GLP-1RA medication; self-reported muscular strength, ability to perform activities of daily living, fatigue, overall health, and quality of life; and perceived barriers and facilitators to resistance training while using a GLP-1RA. Resistance training is assessed using the Muscle-Strengthening Exercise Questionnaire (MSEQ; Shakespear-Druery et al., 2022) Long Form, which captures frequency, session duration, intensity (0-10 OMNI-Resistance Exercise Scale), muscle groups targeted, and type of resistance exercise (weight machines, bodyweight exercises, resistance bands or free weights, and holistic exercises). Items are presented verbatim with the recall anchor adapted from "in a usual week" to "in a usual week BEFORE you started your GLP-1 medication" and "in a usual week SINCE you started your GLP-1 medication" to enable a within-person pre/post comparison.

Consent Electronic informed consent will be obtained at the beginning of the online survey using the IRB-approved online consent script (HRP-537 template). Because the click-to-agree mechanism does not capture a legally valid electronic signature, a Waiver of Documentation of Consent under 45 CFR 46.117(c) has been granted. The research presents no more than minimal risk and involves no procedures for which written consent is normally required outside of the research context.

Privacy and Confidentiality The survey is anonymous. No direct or indirect identifiers (name, email address, IP address) are collected or linked to survey responses. Qualtrics is configured to disable IP address collection and to use anonymous response settings. Data are stored on secure, password-protected Ohio State University servers, in project folders restricted to authorized study personnel listed on the approved IRB protocol. The analytic dataset is anonymous and contains no identifiable components. Consistent with university policy, research data are retained for at least five years after study closure.

Sample Size The target sample size is 200-300 consented participants. This number was selected based on feasibility and the need for sufficient precision to estimate the prevalence of resistance training participation among adults using GLP-1RAs, and to allow exploratory comparisons between participants who do and do not meet resistance training guidelines. Eligibility screening occurs after electronic consent; every consented individual that meets eligibility criteria counts toward the 300-participant enrollment ceiling.

Statistical Analysis Descriptive statistics will summarize participant demographics, GLP-1RA characteristics, and resistance training behaviors. Primary study questions will be addressed using paired analyses comparing resistance training status before and after GLP-1RA initiation. Categorical outcomes will be analyzed using McNemar's test, and continuous or ordinal outcomes using paired t-tests or Wilcoxon signed-rank tests based on data distribution. Associations between resistance training participation and self-reported outcomes (perceived strength, functional capacity, fatigue, quality of life) will be examined using bivariate comparisons and regression analyses. Open-ended responses, if collected, will be grouped using content analysis to identify common barriers and facilitators.

Risks, Benefits, and Compensation The study is minimal risk. The primary foreseeable risk is a potential breach of confidentiality, which is mitigated through anonymous data collection on a secure, institution-approved platform with encrypted transmission and disabled IP-address collection. Participants may experience minor psychological discomfort answering questions about weight, physical activity, or health, and may skip any question or exit the survey at any time. There are no direct medical or therapeutic benefits to individual participants. No compensation is offered.