The Origins of Metformin & Its Historical Context

Metformin, a cornerstone in diabetes treatment today, has a fascinating history that dates back centuries. Extracted from French Lilac, a flower native to the Mediterranean, Metformin’s journey from a medieval remedy to a modern medical marvel is both intriguing and inspiring. This flower, known by various names such as Italian Fitch, Professor Weed, and Goat’s Rue, grows on multiple continents and thrives near aqueducts and water reservoirs.

In medieval Europe, French Lilac was commonly prescribed by herbalists to treat symptoms like excessive urination, thirst, and fatigue, which are now recognized as classic signs of diabetes. Dr. Jean Sterne (1909-1997) a French physician and researcher who is the first physician to prescribe metformin to humans, suggested the name Glucophage (glucose eater). This name has held its place in the jargon of physician circles ever since. Dr. Sterne is the author of a landmark research article in a Moroccan medical journal in 1957, after which metformin emerged as a treatment in human diabetes therapy. He was a multifaceted physician who received specialty training in cardiology, infectious diseases, psychiatry and neurology.

In the post-World War II era, there was considerable interest in metformin due to its antiviral and antimalarial effects. In 1949 it was used in the Philippines as an anti-influenza agent. A substance very similar to metformin called Proguanil, was used to treat malaria. This substance was synthesized after sustained efforts to find a better alternative to Quinine by the British Research Council in the 1930s. 

Only a few decades later (mid 1990s), a groundbreaking clinical study in the United Kingdom took place which allowed for the drug to gain wide trust among physicians. In this study of 5000 participants, also known as UKPDS (United Kingdom Prevention of Diabetes Study), people with diabetes who took metformin had better health outcomes and lived longer compared to those who didn’t take it. This was thought to be due to reductions in the rate of diabetes related complications. These findings marked a critical moment of clarity about how important it is to proactively treat elevations in blood sugar and aim to bring them into a healthy range. It also demonstrated metformin’s superiority in comparison to other oral agents available in the 1990s. Before the UKPDS study, it was common for clinical practice to allow blood glucose levels to be quite high, sometimes reaching over 300 mg/dL, and still consider diabetes to be under “reasonable control.” Thus, the UKPDS was not only pivotal in demonstrating the benefits of tighter glucose control but it also set the stage for a critical reappraisal of long-established clinical practices. This critical reappraisal also  reaffirmed the need for research, development and invention of many additional new treatments (both oral and injectable). Those include modern devices for insulin delivery such as insulin pens, insulin pumps, insulin dermal patches, insulin inhaler devices as well as modern glucose level monitoring devices. The war on the ongoing diabetes epidemic without those new inventions, but more importantly without metformin as a pillar of therapy is practically unthinkable currently.  

By the year 2011, and after 240 years of efforts invested by doctors in researching it and examining its effects, metformin made it on the list of essential medications of the World Health Organization. 

References

1.      CJ Bailey & C Day Practical Diabetes Int 2004; 21(3): 115–117

2.      J Sterne, Wiener Medizinische Wochenshrift 1963. Vol 113, p. 599-602

3.      UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood glucose control with metformin on complications in overweight 

         patients with type 2 diabetes (UKPDS 34). Lancet 1998; 352: 854–865.