GLP-1 receptor agonist-associated weight loss in breast cancer patients receiving concurrent endocrine therapy: a retrospective cohort analysis

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Abstract

[BACKGROUND] Endocrine therapy for hormone receptor-positive breast cancer is associated with adverse metabolic effects - including increased fat mass, decreased lean muscle mass, and insulin resistance - that may attenuate the efficacy of GLP-1 receptor agonists (GLP-1 RAs). This study evaluated GLP-1 RA-associated weight loss outcomes in breast cancer patients receiving concurrent endocrine therapy. [METHODS] We conducted a retrospective cohort analysis of 269 breast cancer patients at a single academic center receiving concurrent GLP-1 RA and adjuvant endocrine therapy. GLP-1 RA and endocrine therapy data were obtained from electronic medication reconciliation lists and pharmacy dispense reports. Patients were required to have initiated GLP-1 therapy during the study period and to have received concurrent GLP-1 RA and endocrine therapy for at least one year. The primary outcome was percentage weight change from GLP-1 initiation to 12 months (± 2 months). Secondary outcomes included proportions achieving ≥ 5%, ≥ 10%, and ≥ 15% weight loss. [RESULTS] Mean one-year percentage weight loss was - 4.5% (95% CI: -6.0% to - 3.0%; -3.9 kg; 95% CI: -4.96 to - 2.93 kg), significantly below the 10-20% observed in postmenopausal subgroups of GLP-1 randomized trials (all p < 0.001). Only 21.3% achieved ≥ 10% and 10.4% achieved ≥ 15% weight loss. Weight loss differed significantly by GLP-1 agent (p = 0.003); semaglutide (- 5.8%) and tirzepatide (- 4.7%) outperformed dulaglutide (+ 0.1%), which is approved for type 2 diabetes only. Higher baseline weight was associated with greater absolute loss (r = - 0.19, p = 0.002), though percentage weight loss did not differ significantly by baseline BMI category (p = 0.303). PR-negative patients lost more than PR-positive patients (- 8.2% vs. -4.2%; p = 0.021, d = 0.46). Type 2 diabetes was present in 70.6% of patients; T2DM status was not significantly associated with weight loss on t-test (p = 0.288), though patients without T2DM were numerically more likely to achieve ≥ 15% loss (21.5% vs. 5.8%). [CONCLUSIONS] GLP-1 RAs produce statistically significant but substantially attenuated weight loss in breast cancer patients on concurrent endocrine therapy. GLP-1 agent selection significantly influences outcomes. Given emerging evidence of oncologic benefit, prospective trials are needed.

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