ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
The Novel Dual GIP and GLP-1 Receptor Agonist Tirzepatide Attenuates Colon Cancer Development by Regulating Glucose Metabolism.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Cancer outcomes and biological mechanisms among patients with type 2 diabetes mellitus using glucagon-like peptide-1 receptor agonists: a systematic review and meta-analysis.Frontiers in oncology · 2026Pooled it
- Spatiotemporal metabolomics of tobacco leaves in response to Pseudomonas syringae infection.Plant physiology · 2026Article
- HIFs: The central drivers of tumors and their role as molecular switches in targeted therapy?Acta pharmaceutica Sinica. B · 2026Review
- Targeting SLC5A2 suppresses colorectal tumour development by enhancing NK cell activity through extracellular vesicle-dependent MICA/B signalling.Clinical and translational medicine · 2026Article
- Nanomedicine-enabled disruption of glucose metabolism and synergistic antitumor therapy.Journal of nanobiotechnology · 2026Review
- Incretin Mimetics in Cancer and Cardiovascular Disease: JACC: CardioOncology State-of-the-Art Review.JACC. CardioOncology · 2026Review
- Article
- The intricate interplay of microbial metabolomics and carcinogenesis: a spotlight on mechanistic pathways, clinical implications and methodological challenges.Frontiers in cellular and infection microbiology · 2026Review
- GLP1 receptor agonism alters growth and therapeutic response in prostate cancer.Endocrine-related cancer · 2025Article
- Haoya Wang Et Al.: Circadian Rhythm Disruption Promotes Tumor Progression Through Upregulated Glycolysis.Cancer medicine · 2025Review
- Metabolic Adaptations in Cancer Progression: Optimization Strategies and Therapeutic Targets.Cancers · 2025Review
- The Novel Dual GIP and GLP-1 Receptor Agonist Tirzepatide Attenuates Colon Cancer Development by Regulating Glucose Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Plakophilin 1 in cancer: context-dependent dualism, subcellular dynamics, and therapeutic targeting.Frontiers in cell and developmental biology · 2025Review
- Spatial profiling of the metabolism-immune axis in ovarian cancer.Frontiers in pharmacology · 2025Review
- Glucagon-like Peptide-1 Receptor Agonists and Colorectal Cancer Risk.AACE endocrinology and diabetesReview
Corrections and comments
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Authors and funding
12 authors.
Funding
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-inducible factor-1 alpha (HIF-1α) with reduced expression and activity of the rate-limiting enzymes 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) and phosphofructokinase 1 (PFK-1). These effects contributed to the downregulation of glycolysis and the tricarboxylic acid (TCA) cycle. TZP also delayed tumor development in a patient-derived xenograft (PDX) mouse model accompanied by HIF-1α mediated PFKFB3-PFK-1 inhibition. Therefore, the study provides strong evidence that glycolysis-blocking TZP, besides its application in treating type 2 diabetes, has the potential for preclinical studies as a therapy for colorectal cancer used either as monotherapy or in combination with other anticancer therapies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.