Metformin is a first-line antihyperglycemic drug: from mechanisms of action to NICE guidelines

March 6, 2023
Specialities :

Diabetes mellitus has been one of the central topics in the field of health care. Well-known international organizations recommend metformin as the main oral antihyperglycemic drug in addition to lifestyle control. The antihyperglycemic effect of metformin is realized in the liver due to a significant reduction in the reserves of pyruvate and dihydroxyacetone phosphate, which are the main substrates of gluconeogenesis. The discovery of metformin’s various pleiotropic activities, including antiviral, antibacterial, anticancer, anti-inflammatory, and antiaging effects, has become the basis for its use in patients with various comorbidities. According to UK National Institute for Health and Care Improvement guidelines, metformin should be considered as a first-line antihyperglycemic drug in overweight and obese patients, as well as in non-overweight patients. Metformin has additional cardioprotective properties, it can be combined with glucagon-like peptide-1 receptor agonists and sodium-dependent glucose co-transporter type 2 inhibitors, and used in concomitant moderate renal failure.


  • 1. IDF Diabetes Atlas. International Diabetes Federation (2021) Tenth edition. Facts & Figures.
  • 2. WHO Diabetes Report (2022)
  • 3. Fox T., Ruddiman K., Lo K.B. et al. (2020) The relationship between diabetes and clinical outcomes in COVID-19: a single-center retrospective analysis. Acta Diabetol., 2020: 1–6. DOI: 10.1007/s00592-020-01592-8.
  • 4. Schlesinger S., Neuenschwander M., Lang A. et al. (2021) Risk phenotypes of diabetes and association with COVID-19 severity and death: a living systematic review and meta-analysis. Diabetologia, 64(7): 1480–1491. DOI: 10.1007/s00125-021-05458-8.
  • 5. IDF Clinical Guidelines Task Force (2006) Global guideline for Type 2 Diabetes: recommendations for standard, comprehensive, and minimal care. Diabet Med., 23(6): 579–593. doi: 10.1111/j.1464-5491.2006.01918.x.
  • 6. American Diabetes Association (2019) Standards of Medical Care in Diabetes-2019 Abridged for Primary Care Providers. Clinical diabetes: a publication of the American Diabetes Association, 37(1): 11–34. doi:10.2337/cd18-0105.
  • 7. Davies M., Aroda V., Collins B. et al. (2022) Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia, 65(12): 1925–1966.
  • 8. NICE (2022) Type 2 diabetes in adults: management.
  • 9. Boltri J., Tracer H., Strogatz D. et al. (2023) The National Clinical Care Commission Report to Congress: Leveraging Federal Policies and Programs to Prevent Diabetes in People With Prediabetes. Diabetes Care, 46(2): e39–e50. doi: 10.2337/dc22-0620.
  • 10. Damanhouri Z., Alkreathy H., Alharbi F. et al. (2023) A Review of the Impact of Pharmacogenetics and Metabolomics on the Efficacy of Metformin in Type 2 Diabetes. Int. J. Med. Sci., 20(1): 142–150. doi: 10.7150/ijms.77206.
  • 11. Nojima I., Wada J. (2023) Metformin and Its Immune-Mediated Effects in Various Diseases. Int. J. Mol. Sci., 24(1): 755. doi: 10.3390/ijms24010755.
  • 12. Al-Kuraishy H., Al-Gareeb A., Alexiou A. et al. (2022) Metformin and growth differentiation factor 15 (GDF15) in type 2 diabetes mellitus: A hidden treasure. J. Diabetes, 14(12): 806–814.
  • 13. Lentferink Y., Knibbe C., Van der Vorst M. (2018) Efficacy of Metformin Treatment with Respect to Weight Reduction in Children and Adults with Obesity: A Systematic Review. Drugs, 78(18): 1887–1901. DOI: 10.1007/s40265-018-1025-0.
  • 14. Sardu C., D’Onofrio N., Torella M. et al. (2019) Pericoronary fat inflammation and Major Adverse Cardiac Events (MACE) in prediabetic patients with acute myocardial infarction: effects of metformin. Cardiovasc. Diabetol., 18: 126. doi: 10.1186/s12933-019-0931-0.
  • 15. Mannucci E., Gallo M., Giaccari A. et al. (2023) Effects of glucose-lowering agents on cardiovascular and renal outcomes in subjects with type 2 diabetes: An updated meta-analysis of randomized controlled trials with external adjudication of events. Diabetes Obes. Metab., 25(2): 444–453. doi: 10.1111/dom.14888.
  • 16. Wang Y., Yu L., Ye Z. et al. (2023) Association of metformin use with fracture risk in type 2 diabetes: A systematic review and meta-analysis of observational studies. Front. Endocrinol. (Lausanne), 13: 1038603. doi: 10.3389/fendo.2022.1038603.
  • 17. He M., Lu B., Opoku M. et al. (2022) Metformin Prevents or Delays the Development and Progression of Osteoarthritis: New Insight and Mechanism of Action. Cells, 11(19): 3012.
  • 18. Liang K., Chen C., Tsai H. et al. (2022) Association Between Oral Metformin Use and the Development of Age-Related Macular Degeneration in Diabetic Patients: A Systematic Review and Meta-Analysis. Invest. Ophthalmol. Vis. Sci., 63(13): 10. doi: 10.1167/iovs.63.13.10.
  • 19. Cao Q., Hu Y., Fu J. et al. (2021) Gestational metformin administration in women with polycystic ovary syndrome: A systematic review and meta-analysis of randomized control studies. J. Obstet. Gynaecol. Res., 47(12): 4148–4157. doi: 10.1111/jog.15044.
  • 20. Li N., Zhou T., Fei E. (2022) Actions of Metformin in the Brain: A New Perspective of Metformin Treatments in Related Neurological Disorders. Int. J. Mol. Sci., 23(15): 8281.
  • 21. Triggle C., Mohammed I., Bshesh K. et al. (2022) Metformin: Is it a drug for all reasons and diseases? Metabolism, 133: 155223. doi: 10.1016/j.metabol.2022.155223.