Journal Article Review Epublish
PubMed: 40805165 DOI: 10.3390/cancers17152466
Metformin Beyond Diabetes: A Precision Gerotherapeutic and Immunometabolic Adjuvant for Aging and Cancer.
Cancers (Basel) 17(15)
Authors: Abdul Rehman, Shakta Mani Satyam, Mohamed El-Tanani, Sainath Prabhakar, Rashmi Kumari, Prakashchandra Shetty, Sara S N Mohammed, Zaina Nafees, Basma Alomar
Affiliations
- Department of Pathology, RAK College of Medical Sciences, RAK Medical and Health Sciences University, Ras Al Khaimah 11172, United Arab Emirates.
- Department of Pharmacology, RAK College of Medical Sciences, RAK Medical and Health Sciences University, Ras Al Khaimah 11172, United Arab Emirates.
- RAK College of Pharmacy, Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah 11172, United Arab Emirates.
- Department of Perfusion Technology, Manipal College of Health Professions, Manipal Academy of Higher Education, Manipal 576104, India.
- Department of Operations, Kasturba Hospital, Manipal Academy of Higher Education, Manipal 576104, India.
- Department of Anatomy, Manipal University College Malaysia, Melaka 75150, Malaysia.
Abstract
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.
MeSH
Diabetes Mellitus, Biguanides, Aging, Neoplasms, Therapeutics, Metformin