Goat’s rue, French lilac, Italian fitch, and professor weed are all names for the same plant: Galega officinalis used in folk medicine to treat diabetes starting in the Middle Ages, maybe earlier. It gave rise to metformin, one of the most popular diabetes medications in the world. In the early 20th century, researchers isolated a compound from G. officinalis called guanidine and chemists found that they could make the compound more tolerable by bonding two guanidines together, forming a biguanide. Metformin is one such biguanide, first synthesized in 1929 and then clinically developed in 1957 by the French physician Jean Sterne, who gave it its first trade name, Glucophage (“glucose eater”). 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.

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 United States, beginning on March 3, 1995. In 2002, metformin became available as a generic medication, making it one of the least expensive diabetes treatments.