Aging Well: Targeting Obesity With GLP-1 Agonists to Enhance Physical and Vascular Health in Postmenopausal Women

Primary outcomes

1. Physical Function Measure: Short Physical Performance Battery (SPPB) score.

   Time frame: 24 weeks

   The SPPB is a standardized test that evaluates lower extremity function using three components: balance tests (standing in various positions), gait speed (walking a short distance), and chair stand (repeated standing from a seated position). Each component is scored from 0 to 4; the total score ranges from 0 to 12. Higher scores represent better physical function.

2. Physical Function Measure: Modified Clinical Test of Sensory Interaction in Balance (mCTSIB) performed on the Rehabilitation Artificial Physical Intelligence Database (RAPID) foot pressure mat

   Time frame: 24 weeks

   The mCTSIB assesses balance under four sensory conditions: eyes open/closed on firm and foam surfaces. Testing is performed while standing on the RAPID foot pressure mat, which captures center of pressure and postural sway data. The primary measure is average sway area of the four sensory conditions. The sway area is the area which is required to correct equilibrium, representing the total area covered by postural sway, measured in square centimeters (cm²).

3. Physical Function Measure: Standing Chest Throw Test with a 2-kg Weighted Ball using Motion Sensor Technology (MST)

   Time frame: 24 weeks

   This test evaluates upper body muscular power. Participants perform a two-handed chest throw of a 2-kg medicine ball from a standing position. The MST is used to record throw distance, velocity, and related performance metrics. The primary measure is Peak Power Score (W).

4. Physical Function Measure: Chair-to-Stand Tests using Motion Sensor Technology (MST)

   Time frame: 24 weeks

   This test assesses lower body strength and function. Participants are instructed to stand up from a chair and sit back down five times without using their arms. The MST measures movement dynamics. The primary measure is peak power score (W).

5. Physical Function Measure: Six-Minute Walk Test (6MWT)

   Time frame: 24 weeks

   The 6MWT is a standardized submaximal exercise test used to assess functional aerobic capacity. Participants are instructed to walk as far as possible in six minutes along a flat, straight course. The total distance walked is recorded in feet. Longer walking distances indicate better aerobic capacity and endurance.

6. Physical Function Measure: Hand Grip Strength using a Hydraulic Hand Dynamometer

   Time frame: 24 weeks

   Participants are instructed to squeeze the dynamometer with maximum effort, measured in kilograms. The highest value from multiple trials is recorded.

7. Physical Function Measure: Short Form-12 (SF-12) Health Survey

   Time frame: 24 weeks

   The SF-12 is a standardized, self-administered questionnaire designed to assess overall health-related quality of life. It includes 12 items that measure physical and mental health components, generating Physical Component Summary (PCS) and Mental Component Summary (MCS) scores. Scores are standardized on a scale where higher values indicate better health status. Both PCS and MCS scores typically range from 0 to 100, with 0 indicating the poorest health and 100 indicating the best possible health status.

8. Physical Function Measure: Patient-Reported Outcomes Measurement Information System (PROMIS) - Fatigue and Physical Function Domains

   Time frame: 24 weeks

   The PROMIS is a standardized set of self-reported questionnaires designed to measure health domains. This study includes the fatigue and physical function domains, which assess the participant's perceived level of tiredness and ability to perform daily physical activities. Responses generate standardized T-scores, calibrated to the general population. Higher fatigue T-scores indicate greater fatigue severity.

9. Aging Biomarkers: Cellular Senescence Markers in Plasma

   Time frame: 24 weeks

   Cellular senescence markers are measured in plasma samples to assess biological aging and cellular stress. These markers may include proteins associated with the senescence-associated secretory phenotype (SASP). Quantification is performed using immunoassays. Higher levels of senescence markers indicate increased cellular senescence.

10. Difference between biological and chronological age

    Time frame: 24 weeks

    Epigenetic clocks estimate biological age by analyzing DNA methylation patterns at specific CpG sites across the genome. Biological age estimates are compared to chronological age to assess aging acceleration or deceleration. Biological age greater than chronological age indicates accelerated biological aging and potential increased risk of morbidity and mortality. Primary measure is the difference (ΔAge) between biological and chronological ages = reported in years.

11. Vascular Function Assessment: Reactive Hyperemia Index (RHI) using EndoPAT

    Time frame: 24 weeks

    The RHI is measured using the EndoPAT device, which assesses endothelial function by evaluating changes in digital pulse volume during reactive hyperemia. This non-invasive test involves occluding blood flow in one arm followed by release to induce vasodilation, with pulse amplitude recorded via finger probes. Lower RHI values suggest endothelial dysfunction and increased cardiovascular risk.