Metformin: Sixty Years of a First-Line Diabetes Medicine

Metformin is one of the most widely used oral medicines for type 2 diabetes, a chronic condition characterised by the body's resistance to insulin and the subsequent inability to properly manage blood glucose levels. For over sixty years, this medicine has been a cornerstone of diabetes management globally. Derived from a traditional herbal remedy, metformin has maintained its place in modern medicine due to its long track record, well-understood effects, and relative affordability. As the global prevalence of type 2 diabetes continues to rise, metformin remains a foundational therapeutic option. It is frequently listed as a first-line choice in clinical guidelines worldwide, including on the World Health Organization’s Essential Medicines List.

From French lilac to the modern pharmacy

The story of metformin begins with a plant known as French lilac or goat's rue (Galega officinalis). For centuries in medieval Europe, traditional healers used preparations of this plant to relieve frequent urination, a classic symptom of diabetes, though the underlying biology of the disease was entirely unknown at the time. The plant contains active compounds called guanidines, which were found in the early 20th century to lower blood sugar. However, early attempts to use these plant extracts directly proved too toxic for human use.

In the 1920s, scientists synthesised safer, related compounds known as biguanides. While the discovery of insulin in the same decade largely overshadowed oral diabetes medicines, French physician Jean Sterne continued researching biguanides. He pioneered the clinical use of metformin in the 1950s, publishing his findings in 1957. It became available in the UK and several European countries in the late 1950s. Interestingly, it took several more decades to be approved in the United States, finally entering the American market in 1995. Today, metformin remains the sole representative of the biguanide class widely used in diabetes care.

Why metformin remains a first-line medicine

Type 2 diabetes is typically managed through lifestyle changes and medicines that help control blood glucose. Metformin works primarily by reducing the amount of glucose produced by the liver and improving the body's sensitivity to insulin, the hormone that helps cells absorb sugar for energy. Unlike some other diabetes medicines, such as sulfonylureas or insulin itself, metformin does not typically cause weight gain and carries a very low risk of causing hypoglycaemia (dangerously low blood sugar).

Because metformin has been in use for so many decades, its long-term safety profile is well-documented. It is generally well-tolerated, though some individuals experience gastrointestinal side effects, and it is not suitable for everyone—such as people with severe kidney impairment, due to a rare but serious condition called lactic acidosis. When a single medicine is not sufficient to reach a patient's targets, guidelines commonly suggest combining metformin with other classes of diabetes drugs. These characteristics, combined with its low cost, are the primary reasons it is commonly recommended as a foundational treatment option in international diabetes guidelines.

The WHO Essential Medicines List and generic availability

The World Health Organization (WHO) maintains an Essential Medicines List (EML), a list updated every two years that identifies medicines considered necessary to meet the priority healthcare needs of a global population. Metformin has long been included on this list as a core medicine for diabetes care. The EML does more than just list the drug; it specifies its clinical use as a first-line therapy for type 2 diabetes, guiding national health policies and procurement.

Because metformin's patents expired long ago, it is available as an unbranded generic medicine worldwide. Generic availability drives market competition, keeping the cost of treatment remarkably low compared to newer, patented diabetes medicines. This makes metformin highly accessible to public health systems and patients in both low- and middle-income countries, allowing millions to manage their condition affordably.

Metformin in South Africa

In South Africa, metformin is classified as a Schedule 4 prescription medicine, meaning it must be prescribed by an authorised medical professional and dispensed under the supervision of a pharmacist. The South African Health Products Regulatory Authority (SAHPRA) is responsible for ensuring that all metformin products registered for sale meet strict standards for quality, safety, and efficacy.

As a widely available generic, metformin is sold under various trade names in South African pharmacies. Because it is a multisource medicine, the Single Exit Price (SEP) mechanism applies, ensuring transparency in what patients pay at the pharmacy counter. Chronic medication is a significant component of healthcare spending in South Africa, making price transparency highly valuable. Patients and healthcare providers can use tools like HealthSA to verify the SAHPRA registration status of specific metformin products and to compare the regulated SEP across different manufacturers.