Efficacy and Safety of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists for Spinal Fusion Outcomes: A Comprehensive Meta-Analysis

Spinal fusion is a widely performed surgical procedure for treating various spinal disorders, with lumbar fusion showing remarkably rapid growth worldwide. Despite positive outcomes after the procedure, it carries significant complications, most notably pseudarthrosis. Compromised blood supply is a key factor disrupting normal bone fusion, making optimal vascularization crucial for successful outcomes. Glucagon-like peptide-1 (GLP-1) receptor agonists, primarily used for diabetes management, demonstrate promising effects including enhanced glycemic control, improved vascular endothelial function, and direct enhancement of osteoblastic cell activity through GLP-1 receptors on bone precursor cells. Theoretically, GLP-1 receptor agonists should be beneficial for optimizing spinal fusion outcomes. We aim to systematically review and analyze the current evidence on the efficacy and safety of GLP-1 receptor agonists in promoting bone fusion and reducing complications in patients undergoing spinal fusion surgery. We conducted a comprehensive systematic review following Cochrane guidelines. We searched PubMed, Web of Science, Scopus, Embase, and Cochrane Library for studies examining GLP-1 receptor agonists in spinal fusion procedures. We used the Newcastle-Ottawa Scale for the quality assessment of the included studies. We conducted a statistical analysis using RevMan 5.4 with risk ratios for dichotomous outcomes. In total, 11 studies with a total of 14,344 participants were analyzed. GLP-1 receptor agonists significantly reduced pseudoarthrosis at six months (risk ratio (RR) = 0.63, 95% confidence interval (CI) = 0.54-0.74) and 12 months (RR = 0.64, 95% CI = 0.57-0.72), and significantly increased acute kidney injury (RR = 1.30, 95% CI = 1.03-1.65). No significant differences were observed for pseudoarthrosis at 24 months (RR = 1.03, 95% CI = 0.53-2.03), readmission rates (RR = 0.85, 95% CI = 0.48-1.51), cerebrovascular accidents (RR = 1.01, 95% CI = 0.63-1.62), and deep vein thrombosis (RR = 1.16, 95% CI = 0.78-1.72). Additionally, no significant reoperations or adverse effects were found. We also performed a subgroup analysis considering the diabetic stage, which showed valuable insights. GLP-1 receptor agonists showed promising results in reducing pseudoarthrosis at short- to medium-term follow-up, indicating potential therapeutic benefits in bone healing applications. However, the increased risk of acute kidney injury suggests the need for careful patient monitoring and risk stratification. The lack of sustained benefit at 24 months and significant heterogeneity observed in several outcomes indicate that further investigation is warranted. Future research should focus on conducting larger, well-designed randomized controlled trials with standardized outcome definitions, longer follow-up periods, and comprehensive safety monitoring to establish optimal dosing protocols and patient selection criteria for GLP-1 receptor agonist therapy in orthopedic applications.