Metformin, a long-established antidiabetic agent, is undergoing a renaissance as a prototype gerotherapeutic and immunometabolic oncology adjuvant. Mechanistic advances reveal that metformin modulates an integrated network of metabolic, immunological, microbiome-mediated, and epigenetic pathways that impact the hallmarks of aging and cancer biology. Clinical data now demonstrate its ability to reduce cancer incidence, enhance immunotherapy outcomes, delay multimorbidity, and reverse biological age markers. Landmark trials such as UKPDS, CAMERA, and the ongoing TAME study illustrate its broad clinical impact on metabolic health, cardiovascular risk, and age-related disease trajectories. In oncology, trials such as MA.32 and METTEN evaluate its influence on progression-free survival and tumor response, highlighting its evolving role in cancer therapy. This review critically synthesizes the molecular underpinnings of metformin’s polypharmacology, examines results from pivotal clinical trials, and compares its effectiveness with emerging gerotherapeutics and senolytics. We explore future directions, including optimized dosing, biomarker-driven personalization, rational combination therapies, and regulatory pathways, to expand indications for aging and oncology. Metformin stands poised to play a pivotal role in precision strategies that target the shared roots of aging and cancer, offering scalable global benefits across health systems.
二甲双胍作为一种历史悠久的抗糖尿病药物，正经历着作为原型老年治疗药物和免疫代谢肿瘤辅助药物的复兴。机制研究进展表明，二甲双胍通过调节代谢、免疫、微生物组介导和表观遗传途径的整合网络，影响衰老和癌症生物学的标志性特征。临床数据现已证实其具有降低癌症发病率、增强免疫治疗效果、延缓多病共存状态及逆转生物年龄标志物的能力。UKPDS、CAMERA等里程碑式研究及正在进行的TAME试验，均揭示了其对代谢健康、心血管风险和年龄相关疾病进程的广泛临床影响。在肿瘤学领域，MA.32和METTEN等试验评估了其对无进展生存期和肿瘤反应的影响，凸显了其在癌症治疗中日益重要的角色。本综述系统整合了二甲双胍多重药理作用的分子基础，审视了关键临床试验结果，并将其与新兴老年治疗药物及衰老细胞清除剂的疗效进行比较。我们探讨了未来发展方向，包括优化给药方案、生物标志物驱动的个体化治疗、合理联合疗法及监管路径，以拓展其在衰老与肿瘤学领域的适应症。二甲双胍有望在针对衰老与癌症共同根源的精准策略中发挥关键作用，为全球医疗系统提供可推广的普惠性健康效益。
肿瘤(癌症)患者之家