Digital Resistance Training for Midlife Women Using GLP-1

Developing a Scalable Digital Resistance Training Intervention to Preserve Muscle Function in Midlife Women Receiving GLP-1 Therapy

The goal of PLAN-RT 1.0 to learn if a 12-week app-based strength training program can help midlife women build and stick with a regular strength training routine while they are taking GLP-1 medication for weight loss. PLAN-RT 1.0 targets women ages 40 to 59 who were not regularly exercising before starting GLP-1 medication.

The main questions this study aims to answer are: (1) Is the PLAN-RT 1.0 program feasible and acceptable to participants (based on how many people join, stay in the study, and use the program)? (2) Does the program lead to early changes in muscle strength, body composition, physical function, and exercise habits?

GLP-1 receptor agonist (GLP-1RA) therapies have emerged as highly effective pharmacological treatments for obesity, yet weight loss achieved through these agents is accompanied by significant lean mass loss. This is particularly relevant for midlife women who are concurrently vulnerable to age- and menopause-related declines in skeletal muscle mass and physical function. Resistance training (RT) is recommended as an evidence-based strategy for preserving lean mass during weight loss treatments, yet no theory-grounded, scalable intervention exists to support RT initiation and maintenance in midlife women. PLAN-RT 1.0 is a 12-week, app-delivered resistance training intervention developed for midlife women (aged 40-59) receiving GLP-1RA therapy for obesity. The intervention integrates three complementary theoretical frameworks - Self-Regulation Theory (initiation), Habit Formation Theory (cue-behavior-reward), and the Affective Response Theory (intrinsic reinforcement) - operationalized through a structured set of behavior change techniques delivered via digital health technologies. This proposed single-arm feasibility pilot (n=15) pursues two specific aims. Aim 1 evaluates the feasibility and acceptability of PLAN-RT 1.0 using pre-specified benchmarks across enrollment, adherence, retention, and ecological momentary assessment (EMA) response rate, alongside exploratory pre-post analyses of body composition, muscle strength and physical function, and behavioral outcomes. Aim 2 examines the mechanistic role of affective response to RT as a driver of habit formation, using EMA-based per-session affective valence data and mixed methods to characterize how GLP-1RA-mediated dopaminergic changes may alter the intrinsic reward signal from exercise. Feasibility benchmarks, variance estimates, and mechanistic insights from PLAN-RT 1.0 will directly inform the development of PLAN-RT 2.0 through an R21 factorial optimization trial (MOST framework) and ultimately an R01 efficacy trial, establishing a scalable clinical tool for lean mass preservation in midlife women receiving GLP-1RA therapy.

Inclusion Criteria: Participants must meet all of the following criteria:

• Female, age 40 to 54 years.
• Recently initiated GLP-1 receptor agonist (GLP-1RA) therapy within the past 6 months.
• Body mass index (BMI) ≥27 kg/m².
• Not currently participating in regular resistance training (self-reported absence of regular resistance training during the previous month).
• Able to stand, sit, and perform bodyweight movements without assistive devices.
• Owns a compatible smartphone (iOS or Android) with cellular or Wi-Fi access and is willing to use study applications.
• Able to read, understand, and provide informed consent in English.
• Willing and able to attend required in-person study visits.

Exclusion Criteria: Participants will be excluded if they meet any of the following criteria:

• Plans to discontinue GLP-1RA therapy or substantially modify treatment during the 12-week study period.
• Self-reported musculoskeletal injury, orthopedic limitation, or surgery within the previous 6 months that would contraindicate resistance training participation.
• Self-reported unstable cardiovascular disease or cardiac event within the previous 6 months.
• Currently pregnant or planning to become pregnant during the study period.
• Active eating disorder or psychiatric condition that may interfere with study participation.
• Unable to use smartphone applications required for the intervention.
• Current participation in another pharmacological, behavioral, weight management, or chronic disease management program that could confound study outcomes.