Tirzepatide cuts long-term pseudoarthrosis and instrumentation failure after lumbar fusion compared to other GLP-1 RAs

Patients undergoing lumbar fusion face risks of mechanical complications like pseudoarthrosis and instrumentation failure, which can necessitate revision surgery. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are known for their metabolic and anti-inflammatory effects, potentially influencing postoperative recovery and bone healing. While traditional GLP-1 RAs target the GLP-1R, tirzepatide uniquely co-activates both GLP-1R and GIPR, demonstrating superior metabolic efficacy. However, its specific impact on spinal fusion outcomes, particularly long-term mechanical stability, has remained largely unexplored.

This retrospective cohort study utilized the TriNetX Global Collaborative Network to compare outcomes in adult patients undergoing lumbar fusion. The exposure groups were defined by a prescription for tirzepatide or other non-tirzepatide GLP-1 RAs within one year prior to surgery. A 1:1 propensity score matching was performed to control for demographic and clinical covariates. Researchers evaluated 90-day medical complications, hospitalizations, and emergency department visits. Long-term mechanical outcomes, specifically pseudoarthrosis, instrumentation failure, and revision surgery, were assessed at 1, 2, and 3 years post-surgery using risk ratios (RRs) with 95% confidence intervals (CIs).

Short-term outcomes, including 90-day medical complications, hospitalizations, and emergency department visits, were similar between the tirzepatide and non-tirzepatide GLP-1 RA groups (P>0.05). At one year post-fusion, rates of pseudoarthrosis (3.0% vs 3.8%), instrumentation failure (1.4% vs 1.7%), and revision surgery (1.3% vs 1.3%) also showed no significant differences (P>0.05). However, significant long-term benefits emerged with tirzepatide use. 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). These protective effects persisted at three years, with pseudoarthrosis remaining significantly lower (3.1% vs 6.0%, RR 0.51, 95% CI 0.32-0.82, P=0.005) and instrumentation failure also reduced (1.6% vs 3.7%, RR 0.43, 95% CI 0.23-0.79, P=0.005). Revision surgery rates remained comparable across all time points.