Metformin Applications in Cancer Treatment and Diabetes Management

Metformin, long established as first-line therapy for type 2 diabetes, is increasingly recognised for its anticancer potential. In diabetes management, its principal actions involve reduction of hepatic gluconeogenesis and improvement of peripheral insulin sensitivity, leading to lower blood glucose and insulin levels. In oncology, metformin exerts pleiotropic effects: activation of the AMP-activated protein kinase (AMPK) signalling axis, suppression of the mammalian target of rapamycin (mTOR) pathway, and modulation of growth factor receptors. These actions collectively inhibit cellular proliferation, induce cell cycle arrest and promote apoptosis. Further, metformin can impair cancer stem cell repopulation and enhance the efficacy of targeted agents. Research spans from mechanistic in vitro studies and novel formulation development to population-level analyses, underscoring global significance for repurposing a well-tolerated, cost-effective drug against diverse malignancies while retaining its central role in glycaemic control.

Research from Nature Portfolio

Recent studies have investigated metformin in combination with targeted inhibitors in bladder cancer models. One seminal report demonstrated that pairing metformin with an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor produced synergistic antitumour effects. Mechanistically, this regimen amplified AMPK activation while concurrently suppressing EGFR-mediated phosphorylation of downstream kinases Akt and ERK. In vitro assays showed marked inhibition of cell proliferation, colony formation and induction of apoptosis. In vivo intravesical administration in an orthotopic murine model yielded significant tumour regression with minimal systemic toxicity, highlighting a promising strategy for locoregional treatment of urothelial carcinoma.

Metformin Applications in Cancer Treatment and Diabetes Management publication trend

The graph below shows the total number of articles in metformin applications in cancer treatment and diabetes management across all publications each year (not limited to Nature Index journals).

Technical terms

AMPK (AMP-activated protein kinase): A cellular energy sensor that, once activated, inhibits anabolic processes and stimulates catabolic pathways to restore energy balance.

mTOR (mammalian target of rapamycin): A serine/threonine kinase that promotes protein synthesis and cell growth; its inhibition can suppress tumour proliferation.

EGFR (epidermal growth factor receptor): A membrane receptor tyrosine kinase involved in cell proliferation and survival signalling; often dysregulated in cancers.

STAT3 (signal transducer and activator of transcription 3): A transcription factor that, when phosphorylated, drives expression of genes promoting cell growth and survival in oncogenesis.

Hydrogel: A three-dimensional, hydrophilic polymer network capable of sustaining drug release and enhancing mucosal adhesion in intravesical therapy.

Orthotopic model: An animal model in which tumour cells are implanted into the organ of origin to mimic the clinical microenvironment and metastatic behaviour.

Recurrence-free survival: The duration after treatment during which a patient remains free from disease recurrence.

Progression-free survival: The interval during which a patient’s disease does not worsen or spread following therapy.

References

1. Metformin-Loaded Chitosan Hydrogels Suppress Bladder Tumor Growth in an Orthotopic Mouse Model via Intravesical Administration. Molecules (2023).
2. Metformin can block precancerous progression to invasive tumors of bladder through inhibiting STAT3-mediated signaling pathways. Journal of Experimental & Clinical Cancer Research (2015).
3. Metformin and gefitinib cooperate to inhibit bladder cancer growth via both AMPK and EGFR pathways joining at Akt and Erk. Scientific Reports (2016).
4. Association of metformin intake with bladder cancer risk and oncologic outcomes in type 2 diabetes mellitus patients. Medicine (2018).