Importance: Patients with #breast cancer (BC) with comorbid #obesity or type 2 #diabetes (T2D) experience poorer survival. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are approved to treat these comorbidities; however, their associations with BC survival and recurrence remain unclear.
Objective: To evaluate the association between GLP-1 RA use and 10-year all-cause mortality and recurrence-free survival (RFS) over the 10-year follow-up period, as well as 5- and 10-year all-cause mortality and RFS probabilities among patients with BC.
Design, setting, and participants: This retrospective cohort study used TriNetX US Collaborative Network data from women (≥18 years) with BC from 68 health care organizations who received a diagnosis between April 1, 2006, and April 1, 2023. Propensity score matching balanced characteristics. Data were analyzed between September 16 and October 3, 2025.
Exposures: GLP-1 RA use (≥2 prescriptions) during the 6 months before and any time after the index diagnosis; nonuse (0 entries).
Main outcomes and measures: The primary outcome was all-cause mortality, and the secondary outcome was RFS. Cox proportional hazards regression model-estimated hazard ratios (HRs) were restricted to 10 years. Kaplan-Meier estimators were used to calculate 5- and 10-year all-cause mortality and RFS probabilities. Prespecified subgroup (postmenopausal) and landmark (6- and 12-month) analyses were conducted.
Results: The study comprised 841 831 eligible patients with BC (mean [SD] age, 69.1 [12.2] years). After exclusions and 1:1 propensity score matching, 3 cohorts were identified: 1610 patients for GLP-1 RA use vs nonuse (patients with obesity [body mass index ≥30]), 2323 patients for GLP-1 RA use vs insulin or metformin (patients with T2D), and 4052 patients for GLP-1 RA use vs sodium-glucose cotransporter 2 inhibitors (patients with T2D). Among patients with obesity, GLP-1 RAs were associated with lower hazard of all-cause mortality (HR, 0.35; 95% CI, 0.21-0.58; P < .001) and RFS (HR, 0.44; 95% CI, 0.30-0.64; P < .001) over a 10-year follow-up period. Among patients with T2D, GLP-1 RAs vs insulin or metformin were associated with lower hazard of all-cause mortality (HR, 0.09; 95% CI, 0.06-0.15; P < .001) and RFS (HR, 0.33; 95% CI, 0.21-0.50; P < .001). No significant differences were observed between GLP-1 RA and sodium-glucose cotransporter 2 inhibitor groups. Subgroup and landmark analyses yielded similar findings.
Conclusions and relevance: In this cohort study of patients with BC, findings suggested a potential association between GLP-1 RA use and improved outcomes among patients with BC who have obesity and related metabolic conditions. These findings support further evaluation of GLP-1 RA therapy in randomized clinical trials
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2848788
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