page_title: Metformin
section_title: History
hierarchical_section_title: Metformin / History
caption_attribution_description: Latina: Galega officinalis
context_page_description: Metformin, marketed under the trade name Glucophage among others, is the first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome. It is not associated with weight gain. It is taken by mouth.
  Metformin is generally well tolerated. Common adverse effects include diarrhea, nausea, and abdominal pain. It has a low risk of causing low blood sugar. High blood lactic acid level is a concern if the medication is used in overly large doses or prescribed in persons with severe kidney problems. It is not recommended in those with significant liver disease. Metformin is generally preferred for gestational diabetes as a first line of treatment over insulin. Metformin is a biguanide antihyperglycemic agent. It works by decreasing glucose production by the liver, by increasing the insulin sensitivity of body tissues, and by exerting an anorexiant effect, thereby reducing caloric intake.
  Metformin was discovered in 1922. French physician Jean Sterne began study in humans in the 1950s. It was introduced as a medication in France in 1957 and the United States in 1995.
context_section_description: The biguanide class of antidiabetic medications, which also includes the withdrawn agents phenformin and buformin, originates from the French lilac or goat's rue (Galega officinalis), a plant used in folk medicine for several centuries. Galega officinalis itself does not contain any of these medications, but isoamylene guanidine; phenformin, buformin, and metformin are chemically synthesized compounds composed of two guanidine molecules, and are more lipophilic than the plant-derived parent compound.
  Metformin was first described in the scientific literature in 1922, by Emil Werner and James Bell, as a product in the synthesis of N,N-dimethylguanidine. In 1929, Slotta and Tschesche discovered its sugar-lowering action in rabbits, finding it the most potent biguanide analog they studied. This result was completely forgotten, as other guanidine analogs, such as the synthalins, took over and were themselves soon overshadowed by insulin.
  Interest in metformin resumed at the end of the 1940s. In 1950, metformin, unlike some other similar compounds, was found not to decrease blood pressure and heart rate in animals. That year, Filipino physician Eusebio Y. Garcia used metformin (he named it Fluamine) to treat influenza; he noted the medication "lowered the blood sugar to minimum physiological limit" and was not toxic. Garcia believed metformin to have bacteriostatic, antiviral, antimalarial, antipyretic and analgesic actions. In a series of articles in 1954, Polish pharmacologist Janusz Supniewski was unable to confirm most of these effects, including lowered blood sugar. Instead he observed antiviral effects in humans.
  French diabetologist Jean Sterne studied the antihyperglycemic properties of galegine, an alkaloid isolated from Galega officinalis, which is related in structure to metformin and had seen brief use as an antidiabetic before the synthalins were developed. Later, working at Laboratoires Aron in Paris, he was prompted by Garcia's report to reinvestigate the blood sugar-lowering activity of metformin and several biguanide analogs. Sterne was the first to try metformin on humans for the treatment of diabetes; he coined the name "Glucophage" (glucose eater) for the medication and published his results in 1957.
  Metformin became available in the British National Formulary in 1958. It was sold in the UK by a small Aron subsidiary called Rona.
  Broad interest in metformin was not rekindled until the withdrawal of the other biguanides in the 1970s. Metformin was approved in Canada in 1972, but did not receive approval by the U.S. Food and Drug Administration (FDA) for type 2 diabetes until 1994. Produced under license by Bristol-Myers Squibb, Glucophage was the first branded formulation of metformin to be marketed in the U.S., beginning on 3 March 1995. Generic formulations are now available in several countries, and metformin is believed to have become the world's most widely prescribed antidiabetic medication.
caption: Galega officinalis, a natural source of galegine
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