Perioperative glucagon-like Peptide-1 receptor agonist use and clinical outcomes following lower extremity fracture fixation: A large retrospective cohort study with two year follow up

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed for Type 2 diabetes and obesity due to their cardiometabolic benefits. However, their effects on fracture healing remain controversial. This study investigates perioperative GLP-1 RA use and outcomes following surgical treatment of lower extremity (LE) fractures. Methods: A retrospective analysis utilizing a large multicenter database compared patients on GLP-1 RAs within one year prior to and after lower extremity index surgery (+GLP) with those not on GLP-1 RAs (–GLP). Propensity score matching was performed on 275,970 included patients, matching 1:1 on age, sex, tobacco use, diabetes mellitus, primary hypertension, hyperlipidemia, chronic ischemic heart disease, chronic lower respiratory disease, and body mass index (BMI), resulting in 6125 “best-matched” patients per group. This was conducted utilizing multivariate logistic regression with a 0.1 caliper. Outcomes were assessed at 1 month, 3 months, and 1 year. Results: At 1-year follow-up, GLP-1 RA users demonstrated a significantly higher rate of nonunion compared to matched controls (5.4% vs 4.4%, Risk Ratio 1.2, 95% CI 1.0–1.4, P < 0.05) when assessing patients who also continued GLP-1 RAs postoperatively. There were no significant differences in wound dehiscence, deep or superficial surgical site infections, or hematoma. Importantly, the +GLP group experienced significantly lower rates of cardiac arrest (0.8% vs 1.6%, RR 0.5, 95% CI 0.3–0.7, P < 0.01) and all-cause mortality (4.4% vs 8.0%, RR 0.5, 95% CI 0.4–0.6, P < 0.01). Conclusions: Perioperative GLP-1 RA use was associated with a higher risk of nonunion following lower extremity fracture surgery, though without increased wound complication rates. Importantly, GLP-1 RA use was linked to reduced cardiac arrest and mortality within one year. These findings suggest that while the increased rate of nonunion is statistically significant, its clinically significance is limited. Thus, the mortality reduction may be more clinically meaningful for patient counseling and perioperative management. Further study is required to clarify the balance between systemic benefits and surgical outcomes of GLP-1 RAs in orthopedic trauma.