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Objectives and questions: Spinal cord injury (SCI) is associated with high morbidity and complex rehabilitation trajectories. Glucagon-like peptide-1 receptor agonists (GLP1-RAs) have demonstrated neuroprotective and anti-inflammatory properties in preclinical models, but their real-world safety and impact in SCI populations remain unclear. The objective of this study is to evaluate and compare the functional and clinical outcomes associated with GLP1-RA use in individuals with SCI, using real-world data from a multi-institutional database.

Material and methods: A retrospective cohort study was conducted using the 2017–2024 data from TriNetX Global Collaborative Network. Adults with SCI were stratified by GLP1-RA use and matched 1:1 (N=268 per group) via propensity scores based on relevant demographic, clinical, and laboratory variables (including age, sex, race, BMI, diabetes, and socioeconomic indicators). The index event was spinal surgery (CPT-coded decompression, instrumentation, or arthrodesis) in patients with a documented SCI diagnosis. Routinely documented clinical data from electronic health records of participating institutions were available for up to one year after the index surgery and extracted through the TriNetX platform for analysis. Primary outcomes included functional status (mobility, spasticity, bladder/bowel dysfunction), opioid use, fatigue, readmission, ICU stay, mortality and complications (UTI, sepsis, DVT, pressure ulcers). Risk differences and Kaplan–Meier survival estimates were used to compare outcomes between the groups.

Results: GLP1-RA use was associated with lower rates of opioid use at 3 months (81.2% vs. 95.5%, p<0.001) and 1 year (85.8% vs. 97.4%, p<0.001). Rates of fatigue (18.3% vs. 25.4%, p=0.047) and readmission (1-year: 63.4% vs. 73.5%, p=0.012) were also reduced in the GLP1RA group. While ICU admissions were lower in the GLP group, the difference was not significant (28.7% vs. 36.2%, p=0.065). There were no significant increases in complications such as infection, wound issues, or mortality. Functional outcomes (mobility, neurogenic dysfunction, sensitivity) remained comparable across groups.

Discussion and conclusions: In this propensity-matched analysis, GLP1-RA use in SCI patients was associated with reduced opioid use, less fatigue, and fewer readmissions without increasing the risk of complications or mortality. These findings support potential benefits of GLP1-RA use in SCI populations and suggest further investigation of potential mechanisms of benefit.