Spine Journal - 2026-09-07 - Journal Article
Impact of GLP-1 Dose Intensity on Perioperative and Long-Term Fusion Outcomes Following ACDF.
Stirpe C, Lee B, Lavu M, Ding I, Furey C, Cheng CW
Topics
Key Takeaway
High-dose GLP-1 RA therapy was not associated with increased pseudarthrosis (4.0% vs 3.8%, p=0.822) or any measured perioperative complication compared to standard-dose GLP-1 RA after ACDF, while both dose groups showed lower pseudarthrosis rates than matched non-users.
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Summary
This retrospective TriNetX database study compared perioperative and fusion outcomes after ACDF in patients on high-dose versus standard-dose GLP-1 RAs, using 1:1 propensity score matching across three pairwise cohorts. No significant differences were found in 90-day readmission (11.4% vs 10.0%), composite complications (9.6% vs 8.9%), dysphagia (10.6% vs 11.2%), or pseudarthrosis (4.0% vs 3.8%) between high-dose and standard-dose groups. Notably, both GLP-1 RA groups demonstrated lower pseudarthrosis rates than matched non-users, suggesting a potential class-level benefit on fusion biology independent of dose intensity.
Key Limitation
Fusion status was inferred from ICD/CPT coding for pseudarthrosis diagnosis and revision posterior cervical fusion rather than confirmed by CT imaging, introducing significant ascertainment bias and likely underestimating true nonunion rates.
Original Abstract
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.