The Novel Dual GIP and GLP-1 Receptor Agonist Tirzepatide Attenuates Colon Cancer Development by Regulating Glucose Metabolism.

ABSTRACT: Colorectal cancer (CRC) is a leading cause of cancer mortality while diabetes is a recognized risk factor for CRC. Here we report that tirzepatide (TZP), a novel polypeptide/glucagon-like peptide 1 receptor (GIPR/GLP-1R) agonist for the treatment of diabetes, has a role in attenuating CRC growth. TZP significantly inhibited colon cancer cell proliferation promoted apoptosis in vitro and induced durable tumor regression in vivo under hyperglycemic and nonhyperglycemic conditions across multiple murine cancer models. As glucose metabolism is known to critically regulate colon cancer progression, spatial metabolomics results revealed that glucose metabolites are robustly reduced in the colon cancer regions of the TZP-treated mice. TZP inhibited glucose uptake and destabilized hypoxia-inducibl

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC12097124 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature