Glenny, E. M.; Ho, A. N.; Kiesel, V. A.; Chen, F.; Gates, C. E.; Paules, E. M.; Xu, R.; Holt, C. A.; Hursting, S. D.

We report for the first time an anticancer benefit of tirzepatide, a dual glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide receptor agonist, in a model of obesity and breast cancer in female mice. Long-term tirzepatide treatment induced weight loss, mitigated obesity-driven changes in circulating metabolic hormone levels, and suppressed orthotopic E0771 mammary tumor growth. Relative to tirzepatide, chronic calorie restriction, an established anticancer intervention in preclinical models, promoted even greater weight loss, systemic hormonal regulation, and tumor suppression. We conclude that tirzepatide represents a promising pharmacologic approach for mitigating the procancer effects of obesity. Moreover, strategies promoting greater weight loss than achieved with tirzepatide alone may augment the anticancer benefits of tirzepatide.