biguanides in diabetes mellitus

IN 1918, Watanabe first demonstrated the hypoglycaemic properties of guanidine. After nearly 40 years of sporadic investigation of its derivatives, including the misadventures with synthalin (Frank, Nothmann & Wagner, 1926), this observation bore clinical fruit in the first of the biguanides, phenylethylbiguanide (phenformin) see Fig. 1). Other biguanides have since appeared including dimethylbiguanide (metformin, 'Glucophage') and butylbiguanide. In the 10 years since their introduction into therapeutics the precise mode of action of these compounds has not been elucidated nor is there complete agreement on the indications for their use. Research and clinical experience have, however, provided both