Fusion Outcomes of GLP-1 Agonist Therapy in Multilevel Cervical Spinal Fusion: A Propensity-Matched Analysis

Study Design: Retrospective analysis. Objective: To evaluate the effects of GLP-1 agonist therapy upon the incidence of pseudarthrosis in patients undergoing multilevel cervical spinal fusion Summary of Background Data: The rising prevalence of obesity and diabetes mellitus has rendered the usage of glucagon-like peptide-1 receptor (GLP-1) agonists increasingly commonplace since their introduction in 2005. However, there is a dearth of evidence to suggest whether outcomes of multilevel cervical spinal fusion differ in patients treated with GLP-1 agonists. This study assesses rates of pseudarthrosis in patients who underwent multilevel cervical spine fusion with and without concurrent GLP-1 agonist therapy. Methods: The TriNetX, LLC Diamond Network database was queried utilizing CPT codes for patients undergoing both anterior and posterior multilevel cervical spinal fusion from 2005 to 2024. Patients prescribed liraglutide, pramlintide, tirzepatide, semaglutide, lixisenatide, or dulaglutide within 1 year of surgery were propensity matched to patients without GLP-1 agonist prescriptions. Cohort balancing was achieved categorically according to age at procedure, race, sex, and nicotine dependence. Cohort balancing was performed continuously to account for body mass index and hemoglobin A1C at the time of procedure. CPT diagnosis codes for pseudarthrosis after attempted fusion were concomitantly utilized to assess pseudarthrosis rates at 6-months, 1-year, and 2-years postoperatively using the Fisher exact test. Statistical significance was set at P<0.05. Results: In consideration of anterior multilevel cervical fusion, 1204 patients utilized GLP-1 agonist therapy, while 1204 patients did not use GLP-1 agonists. With respect to posterior multilevel cervical fusion, 1378 patients utilized GLP-1 agonist therapy, and 1378 patients did not have a GLP-1 agonist prescription. Anterior postoperative pseudarthrosis rates were significantly decreased in the GLP-1 agonist cohort versus the non-GLP-1 agonist cohort at 6-months (10.71% vs. 17.61%; P<0.001), 1-year (12.04% vs. 18.52%; P<0.001), and 2-years (12.87% vs. 19.19%; P<0.001). Posterior postoperative pseudarthrosis rates were also significantly decreased in the GLP-1 agonist cohort versus the non-GLP-1 agonist cohort at 6-months (13.21% vs. 22.28%; P<0.001), 1-year (14.37% vs. 24.45%; P<0.001), and 2-years (16.87% vs. 24.43%; P<0.001). Conclusion: Our findings demonstrate a statistically significant lower incidence of pseudarthrosis among patients treated with GLP-1 agonist therapy at all timepoints within this study - from 6-months to 2-years postoperatively, suggesting a potentially beneficial effect of GLP-1 agonist therapy in promoting fusion success in multilevel cervical spine surgery. Fundamentally, this aligns with the pharmacodynamic nature of GLP-1 agonists: as compounds that enhance osteoblastic activity and suppress osteoclastic activity, thereby facilitating bone formation and attenuating bone resorption. Further investigation into the mechanistic underpinnings of GLP-1 agonists' effects on bone metabolism may pave the way for enhancing the success of cervical spine surgery.