Metformin is an oral anti-diabetic agent. It is the first-line drug of choice for the treatment of type 2 diabetes and has been demonstrated to significantly reduce cardiovascular morbidity and mortality. Metformin does not directly lower blood glucose levels, but by reducing the production of glucose by the liver it can greatly improve glycemic control in Type 2 Diabetes Mellitus (T2DM) patients. Metformin is now widely used in the management of type 2 diabetes and has emerged as one of the most widely prescribed drugs.
Who discovered metformin?
The origin of metformin dates back to the 1920s. The first reports on the use of glucose-lowering properties were published in 1922 by Banting and Best. These researchers observed that animals fed an extract from the leaves of Galega officinalis exhibited reduced blood glucose levels. In 1929, Galega was shown to be capable of lowering blood glucose in diabetic dogs and it was also found that the extract stimulated insulin release from pancreatic beta cells. However, this use as an anti-diabetic drug never reached the market stage.
Metformin was originally discovered by French scientist Jean Sterne who had researched it over a long time. Phenformin was originally used for tuberculosis in 1947, but it was noticed that patients who received the drug had reduced blood glucose levels. However, phenformin had to be taken off the market because it caused lactic acidosis. This occurred when glucose wasn’t able to get into cells so it began producing its energy through anaerobic metabolism. This process creates toxic amounts of lactic acid, which can accumulate in the bloodstream and cause severe injury to multiple organs.
In 1957, metformin was re-synthesized by biguanide chemist James Bell at the Istituto Superiore di Sanità Higher Health Institute under his direction from Dr. Carle LaMontagne. Bell chose to name it metformin because he had discovered it by modifying formamide, a substance in the dihydrofolate-dependent one-carbon metabolic pathway that produces methenamine.
Metformin was trademarked in 1958 and approved for use in France under the trade name “Glucophage” in December 1957 by Rhône-Poulenc Rorer. Its first introduction to clinical research was initiated by the French pharmaceutical company, Laboratoire français de Fractionnement et d’Extraction. Since it was first introduced to the market, metformin has become widely used as an effective treatment for T2DM. Metformin remains under patent today; however, the original patents have expired and generic versions are now available.