Oxoaporphine-Metformin Rhodium(III) Mixed Complex Achieving Dual Antidiabetes and Anticancer Effects by Interfering with Glucose Metabolism Reprogramming

The clinical convergence of type 2 diabetes mellitus (T2DM) and bladder cancer presents a unique therapeutic challenge. We developed a metal-based approach through rational integration of glucose-modulating metformin (<b>Met</b>) with a bioactive oxoaporphine alkaloid in the form of novel rhodium(III) complexes (<b>Rh-Met</b>). This first-reported hybrid metallodrug achieved dual therapeutic efficacy by simultaneously suppressing PI3K/AKT/mTOR signaling to reprogram glucose metabolism in cancer cells and restoring glycemic balance. In a clinically relevant T2DM-tumor model, <b>Rh-Met</b> exhibited a coordination synergistic effect and suppressed tumor progression while reducing hyperglycemia through disruption of energy homeostasis. Our findings demonstrated a paradigm-shifting strategy for concurrent management of diabetes and cancer via precision design of metallodrugs, highlighting the translational potential of metal complexes in comorbid disease therapy.