GLP-1 agonist use and lower rates of pseudarthrosis and dysphagia following anterior cervical discectomy and fusion surgery, with time-dependent effects.

OBJECTIVE: Anterior cervical discectomy and fusion (ACDF) is among the most frequently performed spinal procedures in the US. Despite high success rates, complications such as pseudarthrosis, dysphagia, and revision surgery remain clinically significant, particularly in patients with diabetes mellitus (DM) and obesity. Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) have demonstrated anti-inflammatory and bone-modulating properties in existing clinical and laboratory orthopedic research, yet their relationship to cervical fusion outcomes remains unclear, especially regarding therapy timing. The aim of this study was to evaluate the association between GLP-1 RA use and pseudarthrosis, dysphagia, and revision surgery, as well as perioperative complications, following ACDF surgery.

METHODS: TriNetX, a global health research network, was queried (2014-2024) for patients undergoing ACDF surgery (CPT code 22551) with GLP-1 RA exposure. Subcohort analyses were conducted based on overall therapy timing (preoperative, perioperative, and postoperative) and further stratified by initiation and discontinuation timing. Postoperative initiators were analyzed using a landmark approach to mitigate immortal time bias. Each subcohort was 1:1 propensity score-matched to controls by age, sex, race, smoking, DM, BMI, and uremia. Ninety-day outcomes included deep vein thrombosis, pulmonary embolism, emergency department visit, inpatient hospitalization, sepsis, surgical site infection, and wound disruption. Two-year outcomes included pseudarthrosis, dysphagia, and revision surgery. Odds ratios with 95% confidence intervals were calculated using chi-square analysis.

RESULTS: Among 2345 patients with GLP-1 RA exposure within 2 years after undergoing ACDF, overall use was associated with reduced pseudarthrosis and dysphagia, but not revision surgery. Preoperative GLP-1 RA use was associated with increased odds of dysphagia when discontinued > 12 months before surgery. Continuous perioperative use was associated with increased odds of dysphagia and revision surgery, as well as reduced odds of sepsis. Postoperative initiation was associated with reduced odds of pseudarthrosis and dysphagia in the overall subcohort, reduced odds of pseudarthrosis in patients with DM, and increased odds of dysphagia in those with multilevel fusion surgeries.

CONCLUSIONS: GLP-1 RA use demonstrated timing-dependent associations with outcomes following ACDF surgery. Postoperative initiation of therapy was associated with reduced pseudarthrosis, particularly in patients with DM, and dysphagia, while continuous perioperative exposure increased the risk of dysphagia and revision. These findings suggest a potential role for temporally targeted GLP-1 RA therapy during postoperative healing. Prospective studies are required for validation and to determine causal relationships.