(OR04-05-26) Tirzepatide Improves Metabolic Health but Is Associated With Hepatic Tumor Development in Aged Mice With Triple-Negative Breast Cancer

Saturday, July 25, 2026

9:06 AM - 9:18 AM ET

Location: Maryland Ballroom C

Presenting Author(s)

Evan M. Paules, PhD

Postdoctoral Fellow
Nutrition Research Institute, University of North Carolina at Chapel Hill
Kannapolis, North Carolina, United States

Disclosure(s): Balchem, Inc.: Grant/Research Support (Ongoing)

Co-Author(s)

IT

Isis Trujillo-Gonzalez

Nutrition Research Institute, University of North Carolina at Chapel Hill, United States
JG

Jose-Luis Garduno-Hernandez

Nutrition Research Institute, University of North Carolina at Chapel Hill, United States
ER

Erika Rezeli

University of North Carolina at Chapel Hill, United States
RS

Rani Sellers

University of North Carolina at Chapel Hill, United States
KA

Kristen Atlwegg

University of North Carolina at Chapel Hill, United States
MC

Micheal Coleman

University of North Carolina at Chapel Hill, United States
SH

Stephen D. Hursting

Nutrition Research Institute, University of North Carolina at Chapel Hill, United States

Disclosure(s):

Evan M. Paules, PhD: Balchem, Inc.: Grant/Research Support (Ongoing)

Objectives: Despite the widespread clinical use of tirzepatide for obesity and type 2 diabetes, its effects on cancer prevention and outcomes in aging populations have not been well characterized. In the present study, we evaluated if tirzepatide alters tumor growth in an aged, obese mouse model of triple-negative breast cancer (TNBC).

Methods: Female C57BL/6 mice were studied in young (10 weeks) and aged (17 months) cohorts. After baseline metabolic and functional assessments, mice were randomized to tirzepatide or vehicle and treated every other day for 8 weeks with dose escalation. Mice were then injected with E0771 TNBC cells, and tumor growth was monitored three times weekly. Metabolic measures were reassessed prior to tumor implantation and euthanasia.

Results: Aged obese mice treated with tirzepatide exhibited a 15–20% reduction in body weight, significantly lower circulating glucose, and reduced lean mass with an associated trend toward improved motor coordination. Tirzepatide did not alter tumor growth in aged or young mice; however, hepatic tumors occurred in 40% of aged tirzepatide-treated mice and were absent in vehicle-treated aged controls and all young mice.

Conclusions: Tirzepatide markedly improved metabolic parameters without affecting primary TNBC tumor growth. However, the emergence of hepatic tumors exclusively in aged tirzepatide-treated mice raises concerns of age-dependent effects on liver health. Additional studies are warranted to clarify the hepatic consequences of tirzepatide in aged populations.

Funding Sources: National Cancer Institute, Balchem Corporation (postdoctoral fellowship)