SAT-714 - Losing Pounds, Not Gaining Steps: The Paradox of GLP-1 Receptor Agonist Therapy

Background
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are established therapies for obesity management, with evidence showing that long-term weight control is more effective when combined with regular exercise. However, it is unclear whether individuals become more active after losing weight with GLP-1RAs. To address this uncertainty, we analyzed data from the NIH All of Us Research Program, which links electronic health records with Fitbit activity data, enabling an objective assessment of physical activity patterns.

Methods
We conducted a retrospective pre-post cohort study using the All of Us Research Program, identifying adults with obesity who were initiated on GLP-1 RA therapy (semaglutide, tirzepatide, liraglutide, dulaglutide) and had Fitbit activity data before and after treatment. Primary outcomes included daily step count and moderate-to-vigorous physical activity (MVPA) minutes. Baseline comorbidities were extracted, and paired t-tests were used to assess within-person changes, with one-way ANOVA to compare changes across age groups and independent samples t-test to compare changes between sex and comorbidity subgroups respectively.

Results
Among 1,950 patients with obesity prescribed GLP-1 receptor agonists, 753 (38.6%) had sufficient Fitbit data for analysis. The cohort was predominantly female (78.6%) with a mean age of 52.7 ± 12.9 years. Common co-morbidities included musculoskeletal (MSK) pain (81.9%), hypertension (67.3%), and type 2 diabetes mellitus (48.1%). Following GLP-1 initiation, daily steps decreased significantly from 5,047 ± 3,073 to 4,487 ± 3,133 steps/day (change: -560 ± 2,203; p< 0.001). MVPA declined from 27.9 ± 28.2 to 22.2 ± 23.3 minutes/day (change: -5.7 ± 25.3; p< 0.001; n=570). Subgroup analyses revealed significant sex-based differences: males experienced greater declines in both daily steps (-986 ± 2,244 vs -445 ± 2,180 steps/day; p=0.006) and MVPA (-15.3 ± 34.5 vs -2.9 ± 21.2 min/day; p< 0.001) compared to females. Patients with MSK pain showed significantly greater step reductions than those without (-679 ± 1,911 vs -22 ± 3,165 steps/day; p=0.002). Activity changes did not differ significantly by age group (ANOVA p=0.670 for steps, p=0.819 for MVPA), morbid obesity status (p=0.126), stroke history (p=0.601), or heart failure (p=0.925).

Conclusion
In this real-world cohort, initiation of GLP-1 RA therapy in obese patients led to a significant decrease in daily steps and MVPA, with males and those with MSK pain experiencing the greatest declines. These reductions in activity were not influenced by age, morbid obesity, stroke, or heart failure status. These findings suggest that weight loss alone may not promote increased physical activity, highlighting the need for future studies to explore targeted interventions that encourage physical activity alongside pharmacologic therapy.

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