Metformin (1,1-dimethylbiguanide hydrochloride), is today, the most prescribed oral medicine for type 2 diabetes, taken by millions of people every day. It is inexpensive, effective, and widely available: tablets of 500 mg cost barely a rupee each. For a country where diabetes care is a major household expense, metformin remains one of the few drugs that combines affordability with scientific reliability. Metformin, listed among the World Health Organization’s essential medicines since 2011, is generally safe but may cause mild gastrointestinal upsets, give a metallic taste, or, rarely, may cause lactic acidosis in kidney-impaired patients. Yet its story spans over a century of neglect, rediscovery, and vindication.
The first clue
The roots of metformin can be traced to a herb called Galega officinalis, commonly known as French lilac or goat’s rue. It was used in European folk medicine to treat people who passed sugary urine, an old description of diabetes. In the nineteenth century, chemists analysing the plant discovered that it contained guanidine, a nitrogen-rich compound that could lower animal blood sugar. In 1918, a Japanese scientist named C.K. Watanabe confirmed guanidine’s sugar-lowering property, but its toxicity made it unsuitable for humans. Researchers, therefore, tried to develop safer relatives called “biguanides.” In 1922, two chemists, Emil Werner and James Bell, synthesised one such molecule, “dimethyl-biguanide”, which would later be known as metformin. Ironically, that same year, insulin was discovered in Canada. The world’s attention immediately turned to insulin, which could reverse fatal diabetes in children and young adults almost overnight. In comparison, a mild-acting chemical compound attracted little interest. Metformin quietly disappeared from scientific discussion, going into hibernation.
How it works
Metformin acts as a quiet regulator, unlike insulin, which directly drives glucose into cells. It reduces glucose production in the liver, enhances the body’s sensitivity to insulin, and improves muscle glucose uptake. It also alters the gut microbiome and influences an enzyme called AMP-activated protein kinase (AMPK), often described as the cell’s “metabolic switch.” The result is remarkable: lower blood sugar without weight gain or severe hypoglycaemia.
Accidental rediscovery
The story resumed during the Second World War, when scientists searched for new antimalarial drugs. Some guanidine derivatives were found to lower blood sugar in laboratory animals. In 1949, Filipino doctor, Eusebio Garcia, tested one such compound, metformin, while treating patients for influenza. He noticed that it occasionally reduced blood sugar levels and briefly marketed it as an anti-flu drug named Flumamine. The observation went largely unnoticed, but it later caught the attention of researchers in Europe.
In the 1950s, Jean Sterne, a physician at Aron Laboratories near Paris, came across Garcia’s old reports and wondered whether metformin could be used for diabetes. Working with his colleague Denise Duval, he began to test metformin in animals and later in patients with adult-onset diabetes. The results were promising. Metformin lowered blood sugar modestly, did not cause dangerous hypoglycaemia, and was generally well tolerated. In 1957, Sterne published his findings and proposed the name Glucophage, meaning “sugar-eater.” His work marked the formal birth of metformin as a diabetes drug. It was introduced in France and the United Kingdom, mainly for people with mild, overweight-related diabetes. In the following years, other biguanides such as phenformin and buformin entered the market, offering stronger effects and a higher risk.
During the 1960s and 1970s, phenformin gained wide use, particularly in the United States. However, reports of fatal lactic acidosis, a rare but serious side effect, led to its withdrawal in the late 1970s. The entire class of biguanides fell under suspicion. Though metformin was safer, it was blamed by association. Its use declined sharply, and some experts expected it to vanish completely. However, researchers continued small studies in a few European centres and found that metformin behaved differently from phenformin. The liver did not metabolise it, it was excreted unchanged by the kidneys, and it did not cause a major buildup of lactic acid when prescribed to suitable patients. It helped control blood sugar without causing weight gain or low sugar episodes. These observations kept the drug alive.
Reluctant approval
By the 1980s, researchers recognised that many people with type 2 diabetes were not insulin-deficient but insulin-resistant, meaning their bodies produced insulin but could not use it effectively. Metformin’s ability to counter this resistance made it relevant again. When the French company Lipha sought permission to market it in the United States, the Food and Drug Administration demanded extensive evidence. After almost a decade of review, the drug was finally approved in 1995, nearly forty years after its European launch. Soon afterwards, the United Kingdom Prospective Diabetes Study provided long-term data showing that metformin controlled blood sugar, reduced heart attacks, and improved survival in overweight patients. These results placed it at the centre of diabetes care worldwide.
Cornerstone of Indian care
In India, metformin remains the first-line drug recommended by all major guidelines in type 2 diabetes. It is available through government health schemes and in generic form across private pharmacies. Because it is easy to store, taken orally, and does not require refrigeration or syringes, it fits well within India’s public health system. Metformin helps lower glucose production by the liver and increases the body’s sensitivity to insulin. It can reduce appetite modestly, leading to mild weight loss, and has beneficial effects on cholesterol and blood vessel function. Most people tolerate it well, though some experience stomach discomfort initially. Its major advantage is that it does not cause hypoglycaemia when used alone.
Over the years, researchers have found new uses for metformin beyond blood sugar control. It is widely used in women with polycystic ovary syndrome to improve insulin sensitivity and restore regular cycles, in gestational diabetes during pregnancy in selected cases. Some studies suggest that metformin may delay the onset of type 2 diabetes in high-risk individuals. In recent decades, researchers have observed that people taking metformin for diabetes appear to have lower rates of certain cancers, especially of the colon and breast. Laboratory studies show that the drug influences cell energy pathways that affect cancer growth. Another area of interest is ageing. Scientists studying longevity noticed that animals given metformin lived longer and developed fewer age-related diseases.
(Dr. C. Aravinda is an academic and public health physician. The views expressed are personal. aravindaaiimsjr10@hotmail.com)
Published - November 13, 2025 11:11 am IST
