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These physical barriers likely contribute to treatment resistance and warrant continued investigation of penetration-enhancing strategies tailored to CRC-specific microenvironmental features

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Food and Drug Administration (FDA) in 1994, metformin has become a first-line treatment for type 2 diabetes mellitus (T2DM) ( 2 Materials and methods The literature review was conducted using various databases including Scopus, Web of Science, PubMed, Directory of Open Access Journals (DOAJ), ClinicalTrials.gov, and Science Direct