Metformin has stood as the primary clinical tool for type 2 diabetes for decades, yet its potential reach into oncology and gerontology is only now being critically dissected. This review evaluates how metformin might actually pull the levers of cancer progression and biological aging. Evidence from across various models suggests that the drug works by recalibrating cellular energy homeostasis—specifically by triggering AMPK and dampening the mTOR pathway. This signaling shift ripples through downstream processes like autophagy and oxidative stress regulation, theoretically slowing tumor growth and pushing back against cellular senescence. However, our look at the literature from PubMed, Scopus, and Web of Science shows a messy reality where preclinical success often stalls during clinical translation. Even though observational data point toward lower cancer rates in diabetic cohorts, these “wins” are frequently skewed by clinical confounders and inconsistent data. This makes the leap from metabolic control to a broad-spectrum anti-aging or anticancer therapy a point of serious contention. We argue that only large-scale, randomized trials can truly verify if metformin is safe and effective for non-diabetic populations. In the end, untangling these molecular routes is the only way to see if metformin belongs in future oncological or healthy aging strategies. That being said, at least mechanistically, metformin definitely offers potential that warrants such large-scale research.
Vujovic et al. (2026) studied this question.