What is Metformin?

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Type 2 diabetes mellitus is an ongoing medical issue that clinicians encounter on a daily basis. This condition poses serious health concerns and economic problems, as incidence and prevalence rates continue to rise at alarming rates worldwide. In addition, the need to adequately treat diabetes adequately is crucial due to the myriad of comorbidities and complications associated with uncontrolled diabetes.

As many as fourteen classes of different drugs are available at the moment for the treatment of type 2 diabetes mellitus. The older medications for diabetes – namely insulin and sulfonylureas - are associated with the common side effects of weight gain and hypoglycemia, which can prove costly to the healthcare system. Therefore all risks and benefits should be weighed appropriately when a drug regimen is chosen for a particular individual with diabetes.

Metformin represents a biguanide derivative that improves glucose tolerance in patients with type 2 diabetes by decreasing hepatic glucose production, decreasing intestinal absorption of glucose, and improving insulin sensitivity. During metformin therapy insulin secretion remains unchanged; furthermore, fasting insulin levels and day-long plasma insulin response may actually decrease.

Image Credit: Sonis Photography / Shutterstock
Image Credit: Sonis Photography / Shutterstock

Indications for metformin

Today it is believed that metformin in the most widely prescribed anti-diabetic drug in the world. It is a drug that shows excellent efficacy with favorable weight and lipid profiles, supporting its use as first-line therapy for type 2 diabetes (unless not tolerated or contraindicated). In addition, other beneficial metabolic effects are noted, which include a reduction in cardiovascular disease and mortality when compared with non-intensive treatment.

Several research studies have suggested that metformin has comparable effectiveness and safety to insulin for the treatment of gestational diabetes, and mothers who have used metformin instead of insulin were healthier in the neonatal period. Metformin has been demonstrated to reduce visceral adiposity and insulin resistance after the use of antiretroviral drugs for HIV-infection.

As polycystic ovary syndrome (PCOS) is frequently associated with resistance to insulin, metformin has been proposed as a treatment for this condition since the year 1994. American National Institute for Health and Clinical Excellence recommended that women with PCOS and a body mass index above 25 use this drug for the treatment of anovulation and infertility when other therapies fail to produce acceptable results.

There is evidence that metformin shows direct effects on cancer cells either via insulin reduction or independent of insulin by inhibiting mTOR (protein kinase that directly or indirectly regulates the phosphorylation of hundreds of proteins). It was suggested that this dual activity makes metformin a particularly attractive option for the management of breast cancer, but also for some other cancers (such as colon or pancreatic cancer).

Adverse effects

Metformin has a mostly favorable side-effect profile when prescribed appropriately. As insulin secretion is not affected, the drug is not associated with hypoglycemia when used as monotherapy, but glucose level can drop when used in combination with insulin or sulphonylureas.

The most common adverse reaction is mild gastrointestinal upset with symptoms such as metallic taste, nausea, diarrhea, and abdominal pain, occurring in varying degrees in up to 30% of patients. Most of these are transient in nature and happen when the drug is just introduced or the dose is rapidly increased. Skin rashes are rare, and platelet inhibition does not have any clinical disadvantages.

Lactic acidosis (inadequate clearance of lactic acid from the blood) can be a potential concern with metformin. Still, in a healthy population, it is seldom a problem, and other biguanides (e.g. buformin) cause this condition more often. Underlying medical problems, such as chronic renal disease or myocardial infarction, are well-established risk factors for lactic acidosis.

Even though the usage of metformin can have some drawbacks, its benefits outweigh the risks. Recent research on the nephroprotective activity and its good safety records have resulted in the use of this drug more and more in insulin-resistant states - even before the development of hyperglycemia.


  1. http://journal.frontiersin.org/Journal/10.3389/fphys.2014.00426/full
  2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3737434/
  3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4214027/
  4. http://www.biomedcentral.com/1741-7015/9/33
  5. Stumvoll M, Haring HU, Matthaei S. Metformin. In: Goldstein BJ, Mueller-Wieland D. Type 2 Diabetes: Principles and Practice, Second Edition. CRC Press, Nov 14, 2007; pp. 107-120.

Further Reading

Last Updated: Feb 16, 2021

Dr. Tomislav Meštrović

Written by

Dr. Tomislav Meštrović

Dr. Tomislav Meštrović is a medical doctor (MD) with a Ph.D. in biomedical and health sciences, specialist in the field of clinical microbiology, and an Assistant Professor at Croatia's youngest university - University North. In addition to his interest in clinical, research and lecturing activities, his immense passion for medical writing and scientific communication goes back to his student days. He enjoys contributing back to the community. In his spare time, Tomislav is a movie buff and an avid traveler.


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  1. Angela Del Popolo Angela Del Popolo Italy says:

    The translation of this article is really really poor... you can't understand the real meaning of it. Such an important subject would have surely deserved a better translation!!!


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