Metformin turns 62 in pharmacotherapy: Emergence of non-glycaemic effects and potential novel therapeutic applications

Eur J Pharmacol. 2021 May 5:898:173934. doi: 10.1016/j.ejphar.2021.173934. Epub 2021 Feb 17.

Abstract

Metformin is the most commonly prescribed oral antidiabetic medication. Direct/indirect activation of Adenosine Monophosphate-activated protein kinase (AMPK) and non-AMPK pathways, amongst others, are deemed to explain the molecular mechanisms of action of metformin. Metformin is an established insulin receptor sensitising antihyperglycemic agent, is highly affordable, and has superior safety and efficacy profiles. Emerging experimental and clinical evidence suggests that metformin has pleiotropic non-glycemic effects. Metformin appears to have weight stabilising, renoprotective, neuroprotective, cardio-vascular protective, and antineoplastic effects and mitigates polycystic ovarian syndrome. Anti-inflammatory and antioxidant effects of metformin seem to qualify it as an adjunct therapy in treating infectious diseases such as tuberculosis, viral hepatitis, and the current novel Covid-19 infections. So far, metformin is the only prescription medicine relevant to the emerging field of senotherapeutics. Non-glycemic effects of metformin favourable to its repurposing in therapeutic use are hereby discussed.

Keywords: Cancer; Cardioprotection; Metformin; Obesity diabetes; Renoprotection.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Infective Agents / adverse effects
  • Anti-Infective Agents / therapeutic use*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • COVID-19 / epidemiology
  • COVID-19 Drug Treatment
  • Cardiovascular Diseases / prevention & control
  • Female
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Immunologic Factors / adverse effects
  • Immunologic Factors / therapeutic use*
  • Kidney Diseases / prevention & control
  • Metabolic Syndrome / drug therapy
  • Metformin / adverse effects
  • Metformin / therapeutic use*
  • Obesity / drug therapy
  • Pandemics
  • Polycystic Ovary Syndrome / drug therapy
  • Protective Agents / adverse effects
  • Protective Agents / therapeutic use*
  • SARS-CoV-2

Substances

  • Anti-Infective Agents
  • Antineoplastic Agents
  • Hypoglycemic Agents
  • Immunologic Factors
  • Protective Agents
  • Metformin