Association Between GLP-1RAs and Postoperative Complications Following Operative Ankle Fracture Fixation: A Retrospective Cohort Study

Background: Ankle fractures occur at an estimated rate of 4.22 per 10 000 person-years, occurring most frequently within the 21- to 30-year-old demographic. This retrospective cohort study used the TriNetX research network to evaluate the association between perioperative glucagon-like peptide-1 receptor agonist (GLP-1RA) use and postoperative complications following operative ankle fixation. Methods: Adults were stratified by GLP-1RA exposure (n = 1199 for the 3-month cohort and n = 1397 for both the 6- and 12-month cohorts). These cohorts were balanced via 1:1 propensity score matching for age, race, sex, wound healing risk factors, and diabetes; matching was attempted for body mass index (BMI) and glycated hemoglobin (HbA 1c ) but was not obtained. The 6 complications were assessed from 1 day to 3 months, 6 months, and 1 year postoperatively. Results: Results demonstrated that GLP-1RA therapy was significantly associated with increased risk of hardware failure, beginning at 3 months (log rank test [LRT] χ 2 = 3.838, P = .050) and persisting through 12 months (LRT χ 2 = 5.527, P = .019; risk difference [RD] = 0.017, P = .018). Nonunion/malunion rates in the GLP-1RA cohort were more common, with significance found at 6 months (RD = 0.010, P = .047) and 12 months postoperatively (RD = 0.014, P = .008). No association was observed with postoperative infection across any time point. Furthermore, a neutral significance was established for wound dehiscence and procedural complications. Although test statistics suggested potential variance, primary longitudinal measures did not demonstrate significant divergence between cohorts (12-month LRT P = .131 and P = .482, respectively). Conclusion: These findings suggest that perioperative GLP-1RA use is associated with increased rates of hardware failure and nonunion/malunion, identifying a risk profile localized to osseous integrity. No association was found with postoperative infection, and a neutral significance was established for soft tissue complications. Interpreted in the context of residual imbalance in BMI and HbA 1c , these findings are hypothesis-generating rather than confirmatory. Level of Evidence: Level III, retrospective cohort study.