Glucagon-like Peptide-1 Receptor Agonist Use and Risk of Postmastectomy Lymphedema in Breast Cancer Survivors: A Multicenter Real-World Cohort Study

Purpose Postmastectomy lymphedema is a chronic survivorship complication after breast cancer treatment, particularly among patients exposed to axillary surgery. Obesity and metabolic inflammation are recognized contributors to lymphedema risk. This study evaluated whether glucagon-like peptide-1 receptor agonist exposure was associated with lower incident postmastectomy lymphedema among breast cancer patients undergoing mastectomy and/or axillary procedures. Methods We performed a retrospective cohort study using deidentified electronic health record data from the TriNetX Research Network. Adult patients with breast cancer who underwent mastectomy, axillary lymphadenectomy, sentinel lymph node biopsy, or had acquired absence of breast/nipple were stratified by GLP-1 receptor agonist exposure versus no exposure. One-to-one propensity score matching was used to balance measured baseline characteristics. The primary outcome was incident postmastectomy lymphedema syndrome. Outcomes were assessed from 1 to 650 days after the index event using risk estimates, Kaplan–Meier analysis, and Cox proportional hazards models. Results After propensity score matching, 61,630 patients were included, with 30,815 patients in each cohort. Postmastectomy lymphedema occurred in 258 of 29,259 GLP-1 receptor agonist users and 779 of 30,237 non-users, corresponding to risks of 0.88% and 2.58%, respectively. GLP-1 receptor agonist exposure was associated with lower postmastectomy lymphedema risk in time-to-event analysis (hazard ratio 0.373, 95% CI 0.324–0.429; p < 0.001). The absolute risk difference was − 1.7%, with an estimated number needed to treat of 59. Conclusion In this large real-world breast cancer cohort, GLP-1 receptor agonist exposure was associated with lower coded postmastectomy lymphedema risk over 650 days of follow-up. These findings are hypothesis-generating and support prospective studies evaluating metabolic and anti-inflammatory strategies for lymphedema prevention in breast cancer survivorship. Clinical trial number : Not Applicable