Prehospital glucagon-like peptide-1 receptor agonists are not associated with reduced inpatient opioid exposure but with shorter hospital length of stay after total joint arthroplasty.

AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been hypothesized to confer anti-inflammatory, antinociceptive, and anti-addictive benefits. We aimed to investigate their impact on acute perioperative pain and opioid use after total joint arthroplasty (TJA). METHODS: A retrospective cohort study analyzed 14,375 hip or knee arthroplasties performed between January 2018 and February 2026, which included 882 patients on chronic preoperative GLP-1RA therapy. Using 1:1 propensity-score matching without replacement, 786 GLP-1RA users were matched to 786 non-users (total n=1,572) based on demographics, surgery type, and chronic medication use. RESULTS: In the matched cohort, chronic GLP-1RA use was not associated with reduced inpatient opioid administration (adjusted difference -0.18; 95% CI, -0.74 to 0.38; p=0.53) or corrected postoperative morphine milligram equivalents (MME) (-2.79 MME; 95% CI, -6.95 to 1.37; p=0.19). When normalized to hospitalization time, the difference in inpatient opioid exposure was not statistically significant (+0.073 MME/hour; 95% CI, -0.003 to 0.149; p=0.059). Average visual analog scale (VAS) pain scores also showed no significant difference (-0.094; p=0.15). However, GLP-1RA users demonstrated a consistently shorter length of stay (LOS) (adjusted difference -10.41 hours; 95% CI, -13.97 to -6.85; p<0.001). CONCLUSIONS: Chronic preoperative GLP-1RA therapy was not associated with reduced inpatient opioid exposure or improved early postoperative pain control following TJA. Nevertheless, GLP-1RA use was consistently associated with shorter hospital LOS. Prospective studies are needed to determine whether this finding reflects improved recovery pathways or residual confounding and to evaluate the impact of GLP-1RAs on longer-term postoperative outcomes and opioid utilization.