Do GLP-1 agonists affect perioperative risk in spine surgery? A systematic review and meta-analysis.
BACKGROUND: Use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) is increasing among patients presenting for spine surgery, but their perioperative safety and impact on surgical outcomes, particularly pseudoarthrosis, remain uncertain. METHODS: We conducted a PRISMA-compliant systematic review and meta-analysis (PROSPERO CRD420251111692) of comparative studies enrolling adults undergoing any spine surgery, comparing perioperative GLP-1 RA use with no GLP-1 RA. PubMed, Embase, Web of Science, and EBSCO were searched through August 1, 2025. Two reviewers independently screened, extracted data, and assessed risk of bias with ROBINS-I. Random-effects models were used for dichotomous outcomes, reported as odds ratios (OR) with 95% confidence intervals (CI). Meta-analyses were performed when at least 3 studies reported a given outcome, and outlier studies were excluded from sensitivity analyses. RESULTS: Thirteen retrospective cohort studies were included. Across cohorts, baseline characteristics were broadly similar between GLP-1 users (n = 13,754) and controls (n = 17,591): weighted mean age approximately 61 years, weighted mean BMI in the low-to-mid 30 s, and high prevalence of type 2 diabetes and hypertension. Seven studies evaluating pseudarthrosis showed much heterogeneity, but there was a lower risk with GLP-1 RA use (OR 0.74; 95% CI: 0.55-1.00; p = .049; I2 = 91.7%). This finding was heterogeneous but represented sensitivity analysis (OR 0.64; 95% CI: 0.57-0.73; p < .001; I2 = 45.3%). Pooled analyses found no significant differences for other surgical and nonsurgical outcome measures. There was a nonsignificant trend toward higher nerve injury with GLP-1 exposure (OR 1.57; 95% CI: 0.99-2.48; p = .056; I² = 42.4%). Heterogeneity varied by outcome and was highest for reoperation and utilization endpoints. CONCLUSIONS: In adults undergoing spine surgery, perioperative GLP-1 RA use appears safe and is associated with a nonrobust, lower risk of pseudarthrosis, with no consistent differences in infection, wound, neurologic, thromboembolic, pulmonary, or utilization outcomes. Given confounders and retrospective designs, prospective, agent-specific studies are needed to validate fusion benefits and refine perioperative management.
