GLP-1RAs linked to increased hardware failure and nonunion after operative ankle fracture fixation

Ankle fractures are a common orthopedic injury, frequently requiring operative fixation. While glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly prescribed for type 2 diabetes mellitus and weight management, their perioperative safety profile, particularly concerning bone healing and orthopedic hardware integrity, remains incompletely defined. Previous studies have shown mixed results in soft tissue or hand/wrist surgeries, but the impact on osseous healing in load-bearing joints like the ankle has been largely unaddressed, creating a critical knowledge gap for patients on these medications.

This retrospective cohort study utilized the TriNetX research network to investigate the association between perioperative GLP-1RA exposure and postoperative complications following operative ankle fixation. Adults were stratified into cohorts based on GLP-1RA use (n=1199 for the 3-month cohort; n=1397 for both 6- and 12-month cohorts). These groups were balanced via 1:1 propensity score matching for age, race, sex, wound healing risk factors, and diabetes. Matching for BMI and glycated hemoglobin (HbA1c) was attempted but not achieved. Six specific complications were assessed from 1 day up to 3, 6, and 12 months postoperatively.

Results demonstrated that GLP-1RA therapy was significantly associated with an increased risk of hardware failure, with significance emerging 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 also more common, reaching statistical significance at 6 months (RD=0.010, P=.047) and 12 months postoperatively (RD=0.014, P=.008). No association was observed between GLP-1RA use and postoperative infection across any time point. Furthermore, a neutral significance was established for wound dehiscence and other procedural complications.

At 12 months post-surgery, GLP-1RA users experienced a 1.7% higher risk of hardware failure (P=.018) and a 1.4% higher risk of nonunion/malunion (P=.008) compared to matched controls.