Metformin has a strong claim to being one of the most influential medicines of the past century. For decades, it has underpinned the treatment of type 2 diabetes, helped millions of people control their blood sugar, and inspired a second life in research on everything from ageing and cancer to heart health and fertility.
Its story begins not in a laboratory but in a plant, galega officinalis , also known as French lilac or goat's rue. For centuries, the plant was used in folk remedies for symptoms we now recognise as associated with diabetes, including excessive thirst and frequent urination. In the early 20th century, scientists isolated blood sugar-lowering compounds from it. After years of refinement and testing, metformin emerged as a relatively safe and effective medicine, and was introduced in the UK in the late 1950s.
Large clinical trials , which are carefully designed studies in people to test how well treatments work, confirmed what many doctors already suspected. Metformin was not only effective at lowering glucose, the body's main form of sugar, but also at reducing diabetes-related complications. It became the main treatment for type 2 diabetes across much of the world.
Metformin is a biguanide drug, a class of medicines that lowers blood sugar, and it works by helping the body use insulin more effectively. Insulin is the hormone that helps move glucose from the bloodstream into cells for energy. Metformin reduces the amount of glucose released by the liver, improves the way muscles take up glucose from the blood, and reduces how much glucose is absorbed from food in the gut.
Metformin also activates an enzyme called AMPK , often described as the cell's energy sensor. Enzymes are proteins that help chemical reactions happen in the body.
When AMPK is switched on, it reduces the liver's production of new glucose, a process called gluconeogenesis, and encourages tissues such as muscle to take up and use more glucose. Unlike some other diabetes medicines, metformin does not usually cause weight gain, and on its own it rarely causes low blood sugar.
Beyond diabetes: promise and limits
Metformin's strong reputation has also led researchers to explore possible uses beyond diabetes, although the evidence is mixed. One common off-label use, meaning a medicine is prescribed for a condition it has not officially been approved to treat, is polycystic ovary syndrome (PCOS).
Many people with PCOS have insulin resistance , which means their bodies do not respond properly to insulin and need to produce more of it to keep blood glucose stable. High insulin levels can stimulate the ovaries to produce more androgens, a group of hormones that includes testosterone.
Raised androgen levels can disrupt ovulation and contribute to irregular or absent periods. By improving insulin sensitivity, metformin can help reduce these effects and may help regulate the menstrual cycle.
Metformin has also been studied for its possible effects on ageing and longevity . Although early findings are intriguing, there is still no conclusive evidence that it slows ageing in humans, and it is not approved for that purpose.
Some research has suggested that metformin may have neuroprotective effects, meaning it could help protect the brain and nervous system, particularly with long-term use. But the evidence is inconsistent, and large, long-term clinical trials are still needed to determine whether metformin really can protect against dementia and other neurodegenerative diseases.
These possible uses highlight metformin's versatility, but they also underline the importance of medical oversight. Metformin is generally well tolerated, but like all medicines, it can cause side-effects . The most common are nausea, stomach discomfort, diarrhoea, changes in taste, and loss of appetite. These often improve over time or when people switch to slow-release formulations, which release the drug more gradually. Taking metformin with food can also help.
Another recognised issue is vitamin B12 deficiency , which has repeatedly been observed in people with type 2 diabetes who take metformin. This may happen because the drug reduces how well vitamin B12 is absorbed in the gut.
Over time, low vitamin B12 can lead to anaemia or peripheral neuropathy . Anaemia means the body does not have enough healthy red blood cells to carry oxygen properly, while peripheral neuropathy refers to nerve damage, usually in the hands or feet, that can cause tingling, numbness, pain or weakness.
A rare but serious side-effect is lactic acidosis , a dangerous build-up of lactic acid in the blood. If too much builds up, it can make the blood dangerously acidic and, if untreated, may lead to organ failure. This is more likely in people with severe kidney or liver problems, which is why regular monitoring is important. Healthcare professionals may also advise temporarily stopping metformin before certain medical procedures or if someone becomes severely unwell.
For decades, the advice was simple: start with metformin. In 2026, however, the National Institute for Health and Care Excellence (Nice) updated its guidelines for type 2 diabetes, signalling a move towards earlier and more intensive treatment. The new guidance recommends that most people should be offered an SGLT-2 inhibitor , such as dapagliflozin, alongside metformin from the start.
SGLT-2 inhibitors are drugs that help the kidneys remove excess glucose from the body in urine. This approach aims not only to control blood sugar, but also to protect the heart and kidneys earlier in the course of disease, reflecting a broader shift towards more personalised treatment.
That does not mean metformin has been pushed aside. It remains a cornerstone of diabetes care and is still widely prescribed. But the landscape is changing, and treatment is becoming more tailored to the individual.
Metformin may be old, but it continues to adapt to modern medicine. As diabetes care becomes more personalised and new treatment options emerge, metformin remains a reliable, affordable and effective foundation. Its story is far from over. Sometimes the most transformative medicines are not the newest or the flashiest, but the ones that stand the test of time.
Dipa Kamdar does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.
