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From Metabolism to Longevity: Molecular Mechanisms Underlying Metformin's Anticancer and Anti-Aging Effects

Slavica Vujovic1,2,3, Svetlana Perovic1, Milorad Vlaovic1

  • 1Faculty of Natural Sciences and Mathematics, University of Montenegro, George Washington Street, bb, 81000 Podgorica, Montenegro.

Current Issues in Molecular Biology
|March 28, 2026
PubMed

Insights

Metformin, a type 2 diabetes drug, shows potential for cancer and aging research by regulating cellular energy. However, clinical evidence is mixed, requiring large trials to confirm efficacy in non-diabetic populations.

Area of Science:

  • Oncology
  • Gerontology
  • Metabolic pathways

Background:

  • Metformin is a cornerstone therapy for type 2 diabetes.
  • Emerging research explores its potential anticancer and anti-aging properties.
  • The drug's mechanisms involve cellular energy homeostasis, AMPK activation, and mTOR inhibition.

Purpose of the Study:

  • To critically evaluate metformin's role in cancer progression and biological aging.
  • To review preclinical and clinical evidence supporting its potential oncological and gerontological applications.
  • To assess the translational gap between laboratory findings and clinical outcomes.

Main Methods:

  • Comprehensive literature review of studies from PubMed, Scopus, and Web of Science.
  • Analysis of preclinical data (in vitro and in vivo models).
  • Evaluation of observational and clinical trial data regarding metformin's effects on cancer and aging.

Main Results:

  • Metformin's proposed mechanisms include recalibrating cellular energy, activating AMPK, and dampening mTOR.
  • These pathways theoretically influence autophagy and oxidative stress, potentially slowing tumor growth and senescence.
  • Preclinical successes often fail to translate to clinical benefits.
  • Observational data on reduced cancer rates in diabetic patients are confounded by various factors.

Conclusions:

  • The clinical utility of metformin beyond diabetes treatment, particularly in oncology and gerontology, remains contentious.
  • Significant discrepancies exist between preclinical potential and clinical validation.
  • Large-scale, randomized controlled trials are essential to determine metformin's safety and efficacy in non-diabetic populations for cancer prevention or healthy aging.
Keywords:
AMPKaging-related pathwaysanticancer molecular mechanismsgeroprotectionlongevitymTORmetformin

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