GLP-1 Agonists Increase Risk of Surgical Site Infection and Nonunion in Patients Undergoing Operative Fixation of Ankle Fractures

Research Type: Level 3 - Retrospective cohort study, Case-control study, Meta-analysis of Level 3 studies Introduction/Purpose: Glucagon-like peptide 1 (GLP-1) agonists are an effective medication for glycemic control and weight loss. However, the clinical effects of these medications are unknown in patients undergoing fracture fixation. While GLP-1 agonists have well-established benefits, there is concern that rapid weight loss associated with GLP-1 agonists may lead to malnutrition, increasing the risk of post-operative complications and reduced fracture healing potential. Methods: A retrospective query was performed from January 1, 2010 to January 1, 2022 using an insurance claims database to identify patients undergoing operative fixation of bimalleolar and trimalleolar fractures on GLP-1 agonists (CPT-27814, CPT-27822) (n=4,988). Patients on GLP-1 therapy (n=4,976) at the time of surgery were propensity score-matched 1:1 to controls who were not on GLP-1 agonists (n=4,976) based on age, sex, fracture pattern, procedure type, Elixhauser comorbidity index (ECI) and its individual components. 90-day outcomes were evaluated including medical complications, readmission, and reoperation rates. We also examined the incidence of post-traumatic arthritis, delayed union, and nonunion at 2-year follow-up. Odds ratios (OR) were generated using logistic regression analysis. Results: At 90 days, patients on GLP-1 agonist medications were more likely to develop a surgical site infection (OR 1.69, 95% CI 1.33-2.14) compared to patients without GLP-1 therapy. GLP-1 patients were also at higher risk of wound dehiscence (OR 1.31, 95% CI 1.08-1.58) and reoperation for surgical site infection (OR 1.27, 95% CI 1.10-1.45). However, rates of readmission, deep venous thrombosis, pulmonary embolism, mortality, stroke, myocardial infarction, acute kidney injury and sepsis were comparable regardless of GLP-1 status (p > 0.05). Notably, the GLP-1 group was at higher risk of nonunion (OR 1.65, 95% CI 1.25-2.18) at 2 years postoperatively. Conclusion: When controlling for comorbidities and fracture pattern, GLP-1 agonist use appears to independently increase the odds of wound healing complications, including surgical site infection and wound dehiscence at 90-days. Additionally, patients on GLP-1 therapy were at higher risk of ankle fracture nonunion at 2 years after operative fixation. However, medical complications were similar between groups in the postoperative period. Further investigation is necessary to determine the underlying mechanism of reduced wound and fracture healing potential in patients on GLP-1 agonists.