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GLP-1 Receptor Agonists and Lymphedema Prevention After Axillary Surgery: A Decade of Outcomes from the Largest Single-Center Cohort
Stav Brown
*, Siba Haykal
Yale school of Medicine, New Haven, CT
Background:Lymphedema remains one of the most common and debilitating long-term complications after axillary lymph node surgery, with limited effective prevention strategies. We evaluated the association between GLP-1RA exposure and postoperative lymphedema risk in the largest single-center cohort reported to date.
Methods:A longitudinal cohort study analyzed a decade of outcomes after axillary surgery at a tertiary cancer center. Multivariable logistic regression identified independent predictors of lymphedema while adjusting for age, sex, body mass index (BMI), chemotherapy, radiation therapy, diabetes, and race/ethnicity. Model discrimination and calibration were assessed using receiver operating characteristic analysis and the Hosmer-Lemeshow test.
Results:A total of 15,805 patients undergoing axillary surgery were included, representing the largest single-center cohort analyzed for lymphedema risk. GLP-1RA use was independently associated with a marked reduction in lymphedema risk (OR 0.19, 95% CI 0.146-0.252; p<0.0001), corresponding to an ~80% relative risk reduction. Established risk factors remained significant, including radiation therapy (OR 2.13, 95% CI 1.93-2.34), chemotherapy (OR 2.33, 95% CI 2.09-2.59), and increasing BMI (OR 1.04 per unit, 95% CI 1.03-1.05; all p<0.0001). Male sex was associated with a lower risk (OR 0.52, 95% CI 0.39-0.68; p<0.0001). Model discrimination was good (AUC 0.71, 95% CI 0.69-0.72) with excellent calibration. A female-only analysis (n=15,037) showed nearly identical protective effects of semaglutide (OR 0.19, 95% CI 0.147-0.253; p<0.0001).
Conclusion:In the largest single-center analysis to date spanning a decade, GLP-1RA use was associated with a substantial reduction in lymphedema risk after axillary surgery. These findings support a potential lymphatic-protective role for GLP-1 signaling and identify GLP-1RAs as a promising pharmacologic strategy for perioperative lymphedema prevention.
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