The increasing prevalence of type 2 diabetes mellitus (T2DM) represents a significant public health challenge with serious implications for cancer incidence and treatment. Currently affecting over 400 million individuals worldwide, T2DM is characterized by chronic hyperglycemia and insulin resistance, which contribute to a pro-tumorigenic environment. This review seeks to elucidate the complex relationship between diabetes medications and cancer treatment, emphasizing how various agents, including metformin, sulfonylureas, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, thiazolidinediones (TZDs), and sodium-glucose cotransporter 2 (SGLT2) inhibitors, interact with critical signaling pathways involved in cancer progression. Evidence suggests that these medications can modulate oncogenic pathways such as AMPK/mTOR, insulin/IGF signaling, and Nuclear factor kappa B (NF-κB), leading to either inhibition or stimulation of tumor growth and survival depending on the drug class and biological context. For instance, metformin activates AMPK, inhibiting mTOR and promoting apoptosis, while TZDs exert anti-inflammatory effects that may reduce obesity-related cancer risks. Conversely, some DPP-4 inhibitors have been associated with pro-tumorigenic effects under certain conditions. Given the intricate interplay among diabetes, obesity, and cancer, understanding the effects of antidiabetic therapies on tumor biology is crucial for refining treatment strategies. This review consolidates current findings on the cellular and molecular impacts of major T2DM drug classes on cancer, highlighting their potential benefits and limitations. In conclusion, the findings presented in this analysis are intended to enhance treatment strategies and shape future research initiatives aimed at effectively addressing the complexities of managing patients who are concurrently affected by diabetes and cancer.
