Type 2 diabetes and gynecologic cancers: Immunometabolic convergence and translational implications

Type 2 diabetes mellitus (T2DM) is a highly prevalent chronic condition and an increasingly relevant host factor in cancer prevention, treatment, and survivorship. In gynecologic oncology, clinical observational data link diabetes and broader metabolic dysfunction phenotypes to adverse outcomes in selected malignancies, including HPV-related disease and cervical cancer outcomes, and more consistently reported observational associations in endometrial cancer cohorts. Mechanistically, convergent signaling hubs-insulin/IGF biology, PI3K/AKT/mTOR, and inflammatory circuits such as IL-6/JAK/STAT3 and NF-κB-provide biological plausibility for diabetes-related effects on tumor growth, immune regulation, and treatment response. Persistent hyperglycemia can induce durable immune and epigenetic remodeling consistent with metabolic memory and trained immunity frameworks. Translational evidence is most developed for metformin, including randomized presurgical evaluation in uterine malignancy settings, while other antidiabetic drug classes (e.g., SGLT2 inhibitors and incretin-based biology) have emerging mechanistic and observational oncology-relevant signals that warrant biomarker-driven evaluation. We integrate a targeted narrative synthesis with exploratory transcriptomic and spatial analyses to generate testable hypotheses and propose pragmatic clinical implications and research priorities to support metabolic assessment within gynecologic cancer care pathways.