Weight Loss Patterns and Clinical Outcomes of GLP1 Receptor Agonists in Breast Cancer Survivors

Abstract Use of glucagon-like peptide-1 receptor agonists (GLP1-RA) for weight loss is increasing; implications in breast cancer (BC) survivors remain unclear.This retrospective cohort study evaluated treatment patterns, weight loss, and outcomes in BC survivors at an academic institution receiving GLP1-RA. We evaluated patients with non-metastatic (ductal carcinoma in situ (DCIS), stage 1-3) BC who received GLP1-RA (2005 – 2024). Linear regression models estimated associations between weight change and clinical factors. After excluding DCIS, propensity score matching (1:2) was used to match patients who received GLP1-RA with patients who did not, based on confounding covariates. Kaplan-Meier estimates and log-rank tests compared disease-free survival (DFS) and overall survival (OS) between GLP1-RA users versus non-users in the subgroup with invasive disease. We identified 1,022 patients; 79% had DM2. Median weight and body mass index at GLP1-RA initiation were 86.8 kg (47.2-175.0 kg) and 33.5 kg/m2 (18.9-61.8 kg/m2). In semaglutide or tirzepatide users (442, 43.2%), median weight change at 3, 6, and 12 months after GLP1-RA initiation was −1.9% (−13.2%-14.9%), −3.1% (−20.2%-19.0%), and −2.6% (−27.8%-11.5%), respectively. Endocrine therapy and metformin use were associated with weight gain and loss, respectively; invasive disease stage was linked to greater weight loss. GLP1-RA was not associated with DFS, but OS significantly differed between GLP1-RA users (n=810) and non-users (n=1620) (HR 0.37, 95% CI: 0.27-0.53, p0.0001). In conclusion, in this real-world study in BC survivors, GLP1-RA was associated with modest weight loss and improved all-cause survival. Clinical trials are warranted to study GLP1-RA in this population.