GLP-1 Receptor Agonist Use and Wound Outcomes After Free Flap Breast Reconstruction

Abstract Glucagon-like peptide-1 receptor agonists (GLP-1s) are increasingly used for glycemic control and weight loss, but their impact on surgical wound complications remains unclear. Some studies suggest GLP-1s reduce complications such as infection and dehiscence, while others report increased risk in certain procedures. This study evaluates whether preoperative GLP-1 use is associated with postoperative wound complications in free flap breast reconstruction. We conducted a retrospective cohort study using the TriNetX Research Network, a global database of de-identified health records. Adults (≥18 years) undergoing free flap breast reconstruction (2012–2025) were identified with CPT codes. Patients were stratified into cohorts by GLP-1 use within 1 year before surgery. Prescriptions for semaglutide, liraglutide, dulaglutide, exenatide, or tirzepatide defined GLP-1 users. Cohorts underwent 1:1 propensity score matching, and matched groups were analyzed for wound outcomes. Subgroup analyses were performed by diabetes status. In the pooled cohort, GLP-1 users had significantly lower composite wound complication rates compared with non-users (9.0% versus 17.1%, p = 0.002), including reduced surgical site infections (4.1% versus 8.1%, p = 0.026) and wound dehiscence (3.8% versus 7.8%, p = 0.023). No differences were observed in debridement, seroma, or hematoma rates. In subgroup analyses, GLP-1 use was associated with significantly lower composite wound complications in the non-diabetic subgroup (7.9 versus 18.6%, p = 0.007), while overall complication rates in the diabetic subgroup were comparable between users and non-users. Preoperative GLP-1 use was not linked to increased wound complications and may confer benefit, supporting safety when used perioperatively.