Long-Term Mechanical Complications After Lumbar Fusion in Patients Receiving Tirzepatide vs Other GLP-1 Receptor Agonists.

Abstract

Retrospective cohort study. To compare short-term outcomes and long-term mechanical complications following lumbar fusion in patients receiving tirzepatide versus non-tirzepatide glucagon-like peptide-1 receptor agonists (GLP-1 RAs). GLP-1 RAs have demonstrated metabolic and anti-inflammatory effects that may influence postoperative recovery. Tirzepatide, a dual GLP-1/ glucose-dependent insulinotropic polypeptide (GIP), has shown greater metabolic efficacy than traditional GLP-1 RAs, though its impact on spinal fusion outcomes remains unclear. A retrospective cohort analysis was performed using the TriNetX Global Collaborative Network for adult patients undergoing lumbar fusion. Exposure was defined by tirzepatide or non tirzepatide GLP-1 RAs prescription within one year before surgery. Propensity score matching (1:1) was conducted using demographic and clinical covariates. Ninety-day complications and mechanical outcomes from 1-3 years were evaluated using risk ratios (RRs) with 95% confidence intervals (CIs). After matching, ninety-day medical complications, hospitalizations and emergency department visits were similar between groups (P>0.05). At one year, pseudoarthrosis (3.0% vs 3.8%), instrumentation failure (1.4% vs 1.7%), and revision surgery (1.3% vs 1.3%) were comparable between groups (P>0.05). By two years, tirzepatide was associated with significantly lower pseudoarthrosis (3.1% vs 5.5%, RR 0.56, 95% CI 0.35-0.90, P=0.016) and instrumentation failure (1.5% vs 3.5%, RR 0.42, 95% CI 0.22-0.80, P=0.006), with similar revision rates. At three years, pseudoarthrosis (3.1% vs 6.0%, RR 0.51, 95% CI 0.32-0.82, P=0.005) and instrumentation failure (1.6% vs 3.7%, RR 0.43, 95% CI 0.23-0.79, P=0.005) remained significantly lower, while revision surgery remained nonsignificant. Tirzepatide was associated with comparable short-term safety and lower rates of long-term mechanical complications after lumbar fusion. These findings suggest differences in mechanical outcomes that emerge over extended follow-up and warrant prospective comparative evaluation.