Repurposing metabolic drugs: Anti-diabetic and anti-obesity agents with potential in cancer therapy

Background and aims The growing epidemiological and mechanistic overlap between diabetes, obesity, and cancer has intensified interest in repurposing anti-diabetic and anti-obesity drugs for oncologic applications. Shared pathways including insulin/IGF-1 signaling, chronic inflammation, AMPK/mTOR dysregulation, and metabolic reprogramming suggest that metabolic therapies may influence tumor initiation, progression, and therapeutic response. This review aims to critically evaluate the pharmacological intersections between metabolic drugs and cancer biology, highlighting both therapeutic opportunities and potential risks. Methods A comprehensive narrative synthesis of preclinical studies, clinical trials, epidemiological data, and real-world evidence was conducted to examine the anticancer potential and safety profiles of major anti-diabetic and anti-obesity agents, including metformin, thiazolidinediones, GLP-1 receptor agonists, SGLT2 inhibitors, DPP-4 inhibitors, insulin analogs, and selected weight-loss medications. Mechanistic pathways, tumor-specific effects, hormonal influences, and clinical controversies were analysed within a precision medicine framework. Conclusions Anti-diabetic and anti-obesity drugs demonstrate context-dependent anticancer properties mediated through metabolic and inflammatory signaling pathways; however, their effects vary by tumor type, stage, hormonal context, and patient-specific metabolic characteristics. While agents such as metformin and GLP-1 receptor agonists show promising therapeutic potential, others present safety concerns or tumor-promoting risks under specific conditions. Precision stratification incorporating molecular and metabolic profiling is essential to optimize drug repurposing strategies and guide future tumor-specific clinical trials in the diabesity-oncology research.