The Origins of Metformin
Goat's rue, French lilac, Italian fitch, and professor weed are all names for the same plant: Galega officinalis. This perennial herb, 3 feet tall and with purple, blue, or white flowers, was used in folk medicine to treat diabetes starting in the Middle Ages, maybe earlier. Though it gave rise to metformin, one of the most popular diabetes medications in the world, G. officinalis is now widely considered poisonous. In the early 20th century, researchers isolated a compound from G. officinalis called guanidine, which could lower blood glucose levels in animals but was also toxic. 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 the late 1950s by the French physician Jean Sterne, who gave it its first trade name, Glucophage ("glucose eater").
Two other biguanides—phenformin and buformin—were also produced around this time but later withdrawn because they became associated with lactic acidosis. This condition results from a buildup of lactic acid in the blood, lowering its pH to unhealthy levels. It can be particularly dangerous for people with diabetes. Metformin seemed guilty by association, and the damage done to its reputation meant that metformin took time to catch on, even though it was later shown to trigger lactic acidosis only in rare cases.
Over the next few decades, studies about metformin's safety and efficacy trickled in, but it wasn't until the landmark United Kingdom Prospective Diabetes Study (1977 to 1997) that metformin gained the renown that it enjoys today. In the study, overweight and obese people with type 2 diabetes on metformin lived longer and had fewer heart attacks than those with the same blood glucose levels achieved using insulin or sulfonylureas. In the meantime, the Food and Drug Administration formally approved metformin in 1994, assuring that Americans could have access to this rising star of diabetes care. In 2002, metformin became available as a generic medication, making it one of the least expensive diabetes treatments.