Functional, Cognitive, and Behavioral Correlates of Resistance Training During Tirzepatide-Induced Weight Loss

RESIST-MIND is a prospective, observational, monocentric ancillary study conducted at the TUM Klinikum, Munich, Germany. Active participation in the RESIST trial (protocol code RESIST-26-HAL-0150-I; EU CT number 2026-526200-69-00) is a prerequisite for enrolment. RESIST is a randomized, controlled, open-label Phase IV trial evaluating a structured resistance training program versus usual care in 150 adults with obesity treated with tirzepatide (Mounjaro®) over 24 weeks. RESIST-MIND involves no investigational medicinal product, no intervention, and no randomization. Assignment to resistance training or usual care occurs exclusively within the RESIST trial.

RESIST-MIND adds validated self-administered questionnaires (MFI-20, PSQI, WHODAS 2.0 12-item, FNQ, FCQ-T-reduced, SSK scale; WAI and WPAI in working participants only) and the electronic d2-R Test of Attention at the RESIST baseline visit (V1, Week 0) and end-of-treatment visit (V7, Week 24). Muscle, strength, body composition, anthropometric and patient-reported data are obtained from the RESIST trial database. All endpoints are exploratory and equally ranked, defined as change from V1 to V7. Between-group differences (resistance training vs. usual care) are estimated using linear models adjusted for baseline. Associations between changes in body composition and changes in the ancillary endpoints are examined across both groups using correlation and multiple linear regression. No formal power calculation or multiplicity adjustment is performed.

RESIST participants randomized to the structured resistance training arm of the RESIST trial, receiving tirzepatide and individualized diet and physical activity counselling. Assignment occurs within RESIST, not within this ancillary study.

Behavioral: Structured resistance training · Drug: Tirzepatide

RESIST participants randomized to the usual care arm of the RESIST trial, receiving tirzepatide and individualized diet and physical activity counselling. Assignment occurs within RESIST, not within this ancillary study.

Drug: Tirzepatide

Machine-based structured resistance training over 24 weeks (approx. 3 sessions per week), delivered within the RESIST trial (not part of this ancillary study). Progressive program with an acclimation phase (weeks 1-4) and a target phase (weeks 5-24; 8-12 repetitions at approx. 70-75% 1-RM, with additional eccentric overload from week 9). Sessions are intended to be fully supervised during the first 6 weeks whenever feasible, thereafter at least one supervised session after each interim visit; remaining sessions at the trial site or at partner fitness facilities.

Once-weekly subcutaneous injection over 24 weeks, starting at 2.5 mg/week and increased by 2.5 mg every 4 weeks as tolerated up to a maximum of 10 mg/week, in accordance with the SmPC. Administered within the RESIST trial (not part of this ancillary study).

Plazo: Baseline (Week 0) and end of treatment (Week 24)

Concentration performance and processing speed computed per the d2-R manual from the electronic administration.

Plazo: Baseline (Week 0) and end of treatment (Week 24)

Total score, calculated as the sum of all items.

Plazo: Baseline (Week 0) and end of treatment (Week 24)

Total score, calculated as the sum of all items; higher scores indicate stronger trait food craving (worse outcome).

Plazo: Baseline (Week 0) and end of treatment (Week 24)

Total score, calculated as the sum of all items; higher scores indicate greater disability (worse outcome).

Plazo: Baseline (Week 0) and end of treatment (Week 24)

Five subscale scores (general fatigue, physical fatigue, reduced motivation, reduced activity, mental fatigue), each the sum of its four items; higher scores indicate more fatigue (worse outcome).

Plazo: Baseline (Week 0) and end of treatment (Week 24)

Global score (2-week recall), sum of the seven component scores, range 0-21, analysed as a continuous variable; higher scores indicate worse sleep quality. Analysed as a continuous variable.

Plazo: Baseline (Week 0) and end of treatment (Week 24)

WAI items 1, 2, 6 and 7 (raw responses, analysed individually); WPAI scores: % absenteeism, % presenteeism, % work productivity impairment, % activity impairment. Working participants only.

Plazo: Baseline (Week 0) and end of treatment (Week 24)

Self-concordance index of the Self-Concordance of Sport- and Exercise-related Goals scale (SSK), scored according to the original instructions. Higher scores indicate more self-concordant motivation.

Functional, Cognitive, and Behavioral Correlates of Resistance Training During Tirzepatide-Induced Weight Loss in Adults With Obesity - An Ancillary Study to the RESIST Trial