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

Foot Ankle Orthop · Apr 2026 · Recent

Monteiro SK, Khatri NA, Sari DB, Sanford C

Department of Bioengineering, The University of Toledo, Toledo

Foot & Ankle Orthopaedic Trauma

SUMMARY — THE REDUCTIONGLP-1RA use increases hardware failure and nonunion/malunion risk after ankle fracture fixation without infection increase.
Abstract, as published

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 (HbA1c) 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] χ2 = 3.838, P = .050) and persisting through 12 months (LRT χ2 = 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 HbA1c, these findings are hypothesis-generating rather than confirmatory.

LEVEL OF EVIDENCE: Level III, retrospective cohort study.

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