Metformin

Metformin is one of the most commonly prescribed drugs in the treatment of PCOS.  This is because it addresses the (currently theorised) root cause of PCOS – insulin resistance resulting in hyperinsulinaemia and hyperglycaemia.

How Does Metformin Work?

Metformin works by:

  • Increasing insulin sensitivity at a cellular level, especially enhancing peripheral glucose uptake (ie in your extremities).
  • Suppressing the production of glucose by your liver by more than 1/3.
  • Activating a liver enzyme called AMP-activated protein kinase which is very import in the insulin signalling process, the metabolism of glucose and fats as well as balancing the energy in your body.
  • Decreasing the absorption of glucose from the gastrointestinal tract.
  • Increasing fatty acid oxidation.

A study published in the Annals of Internal Medicine in 2005 by a group of researchers working for the Diabetes Prevention Program Research Group found that in a large group of subjects (over 3200) who had impaired glucose tolerance, defined in this study as being a fasting plasma glucose level of more than 5.3 mmol/L or 95 mg/dL, and 53% of whom already had the metabolic syndrome (being overweight especially with increased central obesity leading to an increase in triglycerides, leading to the production of inflammatory cytokines eventually leading to insulin resistance and often high blood pressure) metformin prevented the development of full blown metabolic syndrome in those who did not already have it by 17% when compared with a placebo.  This sounds good, but compared to an intensive lifestyle program (150 minutes brisk walking a week, a healthy low calorie, low fat diet) it is decidedly inferior.  Diet and exercise prevented the development of full blown metabolic syndrome in those who only had impaired glucose tolerance at the outset of the study by 41%, more than double the protection offered by metformin.

For those participants who already met the criteria for metabolic syndrome at the beginning of the study, lifestyle interventions alone were found to resolve the syndrome in 38% of subjects after three years, compared to only 23% of those taking metformin.

The study also found that participants who took metformin had a much greater incident of gastrointestinal symptoms than those taking a placebo or undertaking the intensive lifestyle program.

Another report of this study in the New England Journal of Medicine finds that lifestyle modification reduces the incidence of diabetes mellitus by 58% compared with a placebo treatment whereas metformin only reduces the incidence by 31%.

Clearly, these results indicate that diet and exercise interventions are far superior to treatment with metformin in treating impaired glucose tolerance.


Orchard TJ, Temprosa M, Goldberg R, et al.: The effect of metformin and intensive lifestyle intervention on the metabolic syndrome: The Diabetes Prevention Program randomized trial. Ann Intern Med 142:611–619, 2005.

http://www.annals.org/cgi/content/full/142/8/611#R5-9

Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM; Diabetes Prevention Program Research Group.  Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.  N Engl J Med. 2002 Feb 7;346(6):393-403.

http://content.nejm.org/cgi/content/full/346/6/393

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