The origin of the antidiabetic medicine metformin in the beautiful French lilac
Figure 1 - Galega officinalis (Wikipedia) with varieties which bloom in shades of white, blue and purple.
Before the development of synthetic chemistry and biotech, the plant world provided most of our useful medicines. The French lilac (Galega officinalis), also known as goat’s rue, has been used in herbal medicine for centuries, perhaps millennia. As with most herbal medicines with a long history of use, the many therapeutic claims made for galega are unvalidated, including its efficacy in epilepsy, pestilence and smallpox. Its use as an agent for increasing lactation in farm animals was so widely accepted that the plant’s name is derived from it (gala (milk) and ega (bring on)).
One clinical application for which there has been convincing scientific data is its use in the management of symptoms, now known to be associated with diabetes, well before the disease was defined.
Clear validation for the use of Galega officinalis in diabetes came in 1914 with the isolation of two of its blood glucose-lowering agents – guanidine, and galegine by the French pharmacist Georges Tanret. Unfortunately, both compounds were too toxic for long-term clinical use. Galegine caused sharp drops in blood pressure and central nervous effects. Medicinal chemists therefore set about synthesising structurally similar molecules to find safer alternatives.
Three related compounds, metformin, phenformin and buformin, that are referred to as biguanides, made it to the market. However, with increasing clinical use, particularly during the 1960s, it became clear that both phenformin and buformin often caused accumulation of blood lactic acid which was potentially fatal. These two drugs were withdrawn in the early 1970s. Metformin survived because it caused the adverse effect only rarely, but the drug nonetheless fell out of favour for a while because many prescribers, particularly in Britain and the USA, saw it guilty by association as a biguanide. However, metformin’s safe use continued in Europe, and the drug was finally approved in the USA in 1994.
The popularity of metformin as a pillar therapy in the management of Type 2 diabetes took a major leap with publication of a landmark study - the UK Prospective Diabetes Study (1977-1997), published in 1998, which studied 1704 overweight (>120% ideal bodyweight) patients with newly diagnosed type 2 diabetes. 753 were included in a randomised controlled trial, with a median duration of over ten years. The study showed that metformin helped such overweight patients live longer with fewer cardiovascular complications and adverse drug reactions compared to those on other oral diabetes drugs. With further supporting clinical trial data te medical community worldwide were convinced that metformin should me a mainstay of treatment of Type-2 diabetes. Over the last financial year over 27 million prescriptions were dispended for metformin in England alone, making it the ninth most widely dispensed medicine. An estimated 600 million to 1.8 billion prescriptions were dispensed worldwide.
Metformin continues to attract much research interest. In 2026, there were 900 scientific publications on it to 20th August. It is already widely used off-license in the management of polyendocrine metabolic ovarian syndrome (previously known as polycystic ovary syndrome; PMOS instead of PCOS). Some researchers, regarding it as a longevity medicine, try to understand how it might work. Others are investigating its potential anticancer effect. With improved understanding of its biochemical mechanisms of action, other potential therapeutic applications will emerge.
If the world of herbal medicines fills us with wonder, we should perhaps remind ourselves of the importance of clinical validation of claimed efficacy. In nature, herbal medicines vary widely in content of active ingredients, making precise dosing difficult. In those circumstances, dosage forms are more convenient, and a synthetic derivative may be more effective and safer. The road to wide acceptance of metformin was a long and tortuous one. Through a series of happy accidents, it has turned out to be a medicine that improves on galegine, the antidiabetic compound naturally present in Galega officinalis.
The author Professor Alain Li Wan Po served as Professor of Pharmaceutics at the Queen’s University of Belfast, and as Professor of Clinical Pharmaceutics at the Universities of Aston in Birmingham and the University of Nottingham. His next contribution to this newsletter will be on
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