GLP-1 receptor agonists and outcomes after cervical spine fusion: a systematic review, meta-analysis, and evidence map of real-world evidence.

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; I2 = 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; I2 = 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.