Metformin is a methyl-biguanide and is a derivative of the French Lilac plant formulated in the 1920’s. Metformin was initially indicated as a treatment for influenza. Ineffective in this role, metformin became a medication in search of a disease over the next two decades.
Years later, metformin was resurrected as a potential treatment for malaria by the French investigator Jean Sterne. During the clinical trials that followed, metformin was serendipitously found to lower glucose. In addition, metformin was well tolerated and had a favorable safety profile. The totality of these issues made metformin unique and allowed metformin to be approved for the treatment of type 2 diabetes in Europe in or around 1957.
The momentum for the use of metformin continued to grow following it’s use in a landmark clinical trial called the United Kingdom Prospective Diabetes Study (UKPDS) in the 1970’s. This study was unique as it asked a simple question “was glucose lowering important in preventing complications commonly seen in type 2 diabetes?” Newly diagnosed patients with type two diabetes were randomized to one of four treatment groups that included three strategies that were deemed intensive, and one was lifestyle only. The metformin group results were unique as it lowered glucose levels, was weight neutral and had a low potential for causing hypoglycemia. More importantly the data suggested a lower rate of cardiovascular events (heart attacks/strokes).
The metformin group consisted of approximately 342 subjects that were obese and newly diagnosed patients with type 2 diabetes. This small group surprisingly suggested cardiovascular benefits not seen in the other three study groups nor in any previous clinical trials. The small numbers in the metformin group spooned optimism but left doubt on the validity of this data. A 10-year follow-up study to the UKPDS (UKPDS 80) suggested a “legacy effect”, that early treatment for glucose and blood pressure decreased complications and once again there was the suggestion of cardiovascular benefits but surprisingly no effects on mortality.
The growing momentum associated with metformin from; European approval, cardiovascular benefits and the long-term “legacy effects” led to the FDA approval of metformin in the United States in 1995.
Within a decade, metformin became the “primary” pharmaceutical agent used in the treatment type 2 diabetes and by 2010 metformin became one of the most widely prescribed medications in the world.