Digital Resistance Training for Midlife Women Using GLP-1

Overview

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.