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Life sciences · Journal article
Supportive Care in Cancer · October 27, 2026
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Abstract 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 incidence of coded postmastectomy lymphedema among breast cancer patients with mastectomy and/or axillary procedure exposure. Methods We performed a retrospective cohort study using deidentified electronic health record data from the TriNetX Research Network. Adult patients with breast cancer and coded mastectomy and/or axillary procedural exposure 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 coded 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. Coded postmastectomy lymphedema occurred in 258 of 29,259 GLP-1 receptor agonist users and 779 of 30,237 non-users, corresponding to incidence rates of 0.88% and 2.58%, respectively. GLP-1 receptor agonist exposure was associated with lower incidence of coded postmastectomy lymphedema 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 surgical/procedural cohort, GLP-1 receptor agonist exposure was associated with lower incidence of coded postmastectomy lymphedema over 650 days of follow-up. These findings are hypothesis-generating and require prospective validation with systematic lymphedema assessment and detailed characterization of GLP-1 receptor agonist timing, duration, dose, and adherence.