European Spine Journal - 2026-08-24 - Journal Article; Review
GLP-1 receptor agonists and outcomes after cervical spine fusion: a systematic review, meta-analysis, and evidence map of real-world evidence.
Yu X, Wang S, Lin K, Guan J
Topics
Key Takeaway
GLP-1RA exposure shows procedure-specific rather than class-wide effects on cervical fusion outcomes, with ACDF pseudarthrosis ORs ranging from 0.52 to 0.86 (inconclusive) while a semaglutide-specific posterior cervical fusion cohort showed OR 4.79 for 2-year pseudarthrosis.
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Summary
This PRISMA-guided systematic review and meta-analysis evaluated GLP-1RA exposure and outcomes after cervical spine fusion across 12 retrospective cohorts published 2025–2026. For ACDF, the TriNetX estimate showed OR 0.52 (95% CI 0.40–0.67) for pseudarthrosis reduction, while the MarketScan estimate was neutral at OR 0.86 (95% CI 0.56–1.32); the pooled ACDF subgroup was OR 0.65 (95% CI 0.40–1.06, I²=74.5%). The overall model was uninformative due to extreme heterogeneity (OR 1.28, 95% CI 0.35–4.70, I²=97.3%), driven by a semaglutide-specific PCF cohort showing markedly higher pseudarthrosis risk (OR 4.79, 95% CI 3.11–7.37).
Key Limitation
I²=97.3% in the overall model renders the pooled OR clinically uninterpretable, and procedure-level subgroup analyses are themselves driven by non-overlapping single-database estimates, meaning no robust class-wide or procedure-wide conclusion can be drawn.
Original Abstract
BACKGROUND
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used for type 2 diabetes and obesity, but their implications for outcomes after cervical spine fusion remain uncertain.
OBJECTIVE
To evaluate the association between GLP-1RA exposure and fusion-related, surgical, and medical outcomes after cervical spine fusion.
METHODS
We conducted a PRISMA-guided systematic review, meta-analysis, and evidence map of GLP-1RA/incretin-based therapy exposure in cervical fusion or cervical decompression-and-fusion cohorts. PubMed/MEDLINE, Embase, Web of Science Core Collection, CENTRAL, and Scopus were searched from inception to 1 June 2026. Because several studies used overlapping databases, double-counting decisions were prespecified, and prioritized non-overlapping estimates were used for primary pseudarthrosis synthesis.
RESULTS
Twelve retrospective cohorts published in 2025-2026 were included. In the primary pseudarthrosis synthesis, a combined TriNetX ACDF estimate was associated with lower odds of pseudarthrosis among GLP-1RA-exposed patients (OR, 0.52; 95% CI, 0.40-0.67), whereas an independent MarketScan ACDF estimate showed a neutral association (OR, 0.86; 95% CI, 0.56-1.32). The ACDF subgroup estimate was 0.65 (95% CI, 0.40-1.06; I 2 = 74.5%). Conversely, a semaglutide-specific PCF cohort showed higher 2-year pseudarthrosis (OR, 4.79; 95% CI, 3.11-7.37). The overall model showed substantial heterogeneity (OR, 1.28; 95% CI, 0.35-4.70; I 2 = 97.3%), supporting procedure-specific rather than class-wide interpretation.
CONCLUSIONS
Observational evidence suggests procedure-specific rather than class-wide associations after cervical spine fusion. For anterior cervical surgery/ACDF, evidence was collectively inconclusive, with estimates ranging from lower-risk to neutral, whereas a semaglutide-specific PCF cohort showed higher pseudarthrosis and dysphagia signals. These findings are hypothesis-generating and require validation in procedure-specific studies.