SUN-730 - Association of Semaglutide Use for Weight Management and 1-Year Changes in Frailty Status in A U.S. Veterans Cohort

Background:

Frailty is a highly prevalent and clinically significant geriatric syndrome, strongly linked to disability, hospitalization, and mortality among adults ≥65 years and increasingly recognized in adults with obesity and metabolic disease. The Veterans Affairs Frailty Index (VA-FI), a deficit accumulation measure derived from 31 clinical variables, is a validated tool for assessing frailty in the VA health system. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for diabetes and weight management; despite their metabolic benefits, their effect on overall frailty remains unclear. We examined the association between semaglutide therapy for weight loss and changes in frailty over 1 year using the VA Frailty Index.
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Methods
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We conducted a retrospective cohort study using data from the VA Informatics and Computing Infrastructure (VINCI). U.S. Veterans prescribed semaglutide for weight management between January 2023 and August 2024 (N = 12,810) were included. Frailty status at baseline and one-year follow-up was determined using the VA Frailty Index (VA-FI), which categorizes Veterans as Robust (≤0.10), Prefrail (0.10–0.20), or Frail (>0.20). VA-FI domains include chronic medical conditions, functional status, sensory impairment, cognitive and mood disorders, and other geriatric syndromes. Changes in frailty status and individual health domains were evaluated using McNemar tests, with p < 0.05 considered statistically significant. Analyses were performed using R version 4.5.1.

Results:

Patients had a mean age of 55.8 ± 12.0 years; 20.2% were < 45 years, the largest group was 55–64 years (30.4%), and 65.8% were male. At baseline, 47.7% were robust, 36.0% were prefrail, and 16.3% were frail. At one-year follow-up, 48.8% were robust, 34.0% were prefrail, and 17.2% were frail (p < 0.001 for overall change). Several conditions increased in prevalence, including diabetes (22.1% to 24.1%; p < 0.001), hypertension (57.2% to 61.6%; p < 0.001), kidney disease (7.0% to 9.0%; p < 0.001), and liver disease/cirrhosis (1.3% to 1.6%; p = 0.026). In contrast, select conditions declined, including incontinence (6.2% to 5.3%; p < 0.001) and mood disorders (47.2% to 46.2%; p = 0.011).

Conclusion:

In this large national Veterans cohort, frailty trajectories following semaglutide initiation were heterogeneous at 1 year. While some individuals demonstrated progression from prefrailty to frailty, others showed improvement, including transitioning from prefrail to robust, which is not typically expected in deficit accumulation models. These findings suggest variable frailty responses to GLP-1 receptor agonist therapy and support the need for comparator groups and prospective studies to better define the longitudinal effects of weight-loss pharmacotherapy on frailty and functional aging.

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