[4] Examples include: Galega officinalis (French lilac) was used in diabetes treatment for centuries.

Initially phenformin was widely used, but its potential for sometimes fatal lactic acidosis resulted in its withdrawal from most pharmacopeias (in the U.S. in 1978).

[citation needed] Biguanides do not affect the output of insulin, unlike other hypoglycemic agents such as sulfonylureas and meglitinides.

The most important and serious side effect is lactic acidosis, therefore metformin is contraindicated in advanced chronic kidney disease.

[citation needed] During WWII a British team led by Frank Rose discovered (see details there) that some biguanides are useful as antimalarial drugs.

Much later it was demonstrated that they are prodrugs metabolised into active dihydrotriazine derivatives which, until recently, were believed to work by inhibiting dihydrofolate reductase.