Diabetes and Cancer-Pathophysiology and Clinical Implications: A Systematic Review

Diabetes Mellitus and cancer are major global health problems with rising incidence worldwide. This systematic review was conducted following PRISMA 2020 guidelines by searching PubMed, Scopus, ScienceDirect, SpringerLink, and Google Scholar for studies published between 2015 and 2026. Studies investigating the association between diabetes mellitus and cancer were selected based on predefined criteria, and data were synthesized using a narrative approach. The findings indicate a strong and mechanistically complex association between diabetes mellitus and multiple cancers, particularly pancreatic, breast, colorectal, and prostate cancers. Hyperglycemia, insulin resistance, and chronic inflammation are consistently implicated in tumor initiation and progression through key signaling pathways, including Wnt/β-catenin, PI3K/AKT/mTOR, and AMPK. A bidirectional relationship is most evident in pancreatic cancer, highlighting its unique metabolic and oncogenic interplay. Shared molecular mediators such as cytokines, microRNAs, and metabolic regulators further support a common pathogenic link. Metformin, an antidiabetic drug, demonstrated potential anticancer effects via modulation of these interconnected pathways. Overall, this review underscores a biologically intertwined relationship between diabetes mellitus and cancer, supporting the development of integrated therapeutic strategies targeting shared metabolic and signaling mechanisms.