Exploring Terpenoids as Dual-Action Agents in Diabetes and Cancer: A Review of Their Anti-Hyperglycemic, Anti-Glycolytic Actions, and Combination Therapy Potential.

Cancer and diabetes represent a dual health burden linked by shared metabolic disturbances, particularly hyperglycemia and glycolytic reprogramming. This metabolic overlap highlights the need for agents capable of modulating both conditions simultaneously. Terpenoids have emerged as promising candidates, and this review synthesizes evidence on six representative compounds-beta-caryophyllene, carvacrol, zerumbone, limonene, beta-elemene, and thymol-demonstrating their ability to lower blood glucose levels (anti-hyperglycemic) and suppress tumor metabolism (anti-glycolytic). Among these, zerumbone, beta-caryophyllene, and carvacrol consistently show the strongest dual activity by targeting the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR), glucose transporter 4 (GLUT4), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)/signal transducer and activator of transcription 3 (STAT3) signaling pathways. By contrast, limonene, beta-elemene, and thymol exhibit asymmetric evidence, with stronger activity in either diabetes or cancer models. To translate these biological effects into clinical outcomes, nanocarrier formulations are required to overcome inherent pharmacokinetic barriers. Furthermore, the synergistic potential of these terpenoids when combined with conventional agents such as metformin and cisplatin underscores a significant translational opportunity to improve efficacy while reducing systemic toxicity. Ultimately, by targeting the shared PI3K/AKT/mTOR axis, these dual-function agents restore glucose homeostasis while suppressing tumor glycolysis. This integrated mechanistic approach supports a promising, yet underexplored, combination therapy strategy that warrants further translational investigation.