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Impact of GLP-1 Dose Intensity on Perioperative and Long-Term Fusion Outcomes Following ACDF
Collin Stirpe1, Brandon Lee2, Monish Lavu1
1Department of Orthopedic Surgery, University Hospitals/Case Western Reserve University, Cleveland, Ohio, USA.
Background Context:
High-dose glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used for obesity management, but their perioperative safety and potential effects on fusion-related outcomes after anterior cervical discectomy and fusion (ACDF) remain unclear.
Purpose:
To compare short-term postoperative outcomes and longer-term fusion-related outcomes after ACDF among patients receiving high-dose versus standard-dose GLP-1 RA therapy.
Study Design/Setting:
Retrospective cohort study using the TriNetX Research Network.
Patient Sample:
Adult patients undergoing ACDF were identified within TriNetX and stratified into 3 pairwise comparison groups: standard-dose GLP-1 RA versus no GLP-1 exposure, high-dose GLP-1 RA versus no GLP-1 exposure, and high-dose versus standard-dose GLP-1 RA use. A total of 112,065 patients met inclusion criteria across all 3 comparisons. In the primary dose-intensity comparison, 921 patients remained in each cohort after 1:1 propensity score matching.
Outcome Measures:
Outcomes included 90-day healthcare utilization (readmission, emergency department visits, outpatient visits, physical therapy utilization), 90-day medical and acute postoperative complications, 90-day opioid exposure, and long-term fusion-related outcomes from 180 to 720 days, including pseudarthrosis and posterior cervical fusion.
Methods:
Data were queried on March 9, 2026. Adults undergoing ACDF were identified and stratified by preoperative GLP-1 RA dose intensity. Exposure was defined by recorded GLP-1 RA prescription strength from 1 year to 1 week before the index ACDF procedure. Separate 1:1 propensity score matching was performed for each pairwise comparison. Outcomes were evaluated at 1 to 90 days for healthcare utilization, short-term complications, and opioid exposure, and at 180 to 720 days for long-term fusion-related outcomes.
Funding/Conflicts Of Interest:
No funding was received for this study. The authors report no study-specific conflicts of interest or associated biases.
Results:
In the primary high-dose versus standard-dose comparison, 90-day healthcare utilization was similar, including readmission (11.4% vs 10.0%; p = 0.327), emergency department visits (11.4% vs 12.3%; p = 0.564), outpatient visits (49.8% vs 52.1%; p = 0.328), and physical therapy utilization (42.0% vs 44.0%; p = 0.397). Short-term complications were also similar, including composite medical complications (9.6% vs 8.9%; p = 0.629), dysphagia (10.6% vs 11.2%; p = 0.709), hematoma (6.8% vs 6.3%; p = 0.638), dysphonia (1.8% vs 1.6%; p = 0.721), and acute respiratory failure (2.3% vs 1.7%; p = 0.406). Opioid exposure did not differ between cohorts (85.2% vs 83.1%; p = 0.202). Long-term outcomes were likewise similar, including pseudarthrosis (4.0% vs 3.8%; p = 0.822) and posterior cervical fusion (3.0% vs 3.7%; p = 0.398). Compared with matched non-users, both standard-dose and high-dose GLP-1 RA users had lower pseudarthrosis rates, although no additional long-term benefit was observed with higher-dose therapy.
Conclusions:
High-dose GLP-1 RA therapy was not associated with increased short-term healthcare utilization, postoperative complications, opioid exposure, or long-term fusion-related risk after ACDF compared with standard-dose therapy. These findings provide reassurance that higher-dose GLP-1 regimens do not appear to confer excess perioperative or fusion-related risk in this population.