Metformin has been on the market for over 65 years. It was first sold in France in 1959 under the brand name Glucophage, and it received FDA approval for the U.S. market on March 3, 1995. That three-decade gap between European and American availability is one of the more unusual stories in modern pharmacy.
From Medieval Herb to Modern Drug
Metformin’s roots go back centuries. In medieval Europe, herbalists used a plant called Galega officinalis, commonly known as French lilac or goat’s rue, to relieve the intense urination associated with diabetes. The plant’s active component, guanidine, was eventually isolated and used to create synthetic compounds in the early 19th century, but those early versions proved too toxic for safe use.
Chemists eventually figured out that linking two guanidine molecules together (creating what’s called a biguanide) produced compounds that lowered blood sugar more safely. Metformin is one of those biguanides. In 1957, French physician Jean Sterne conducted the first clinical trials of metformin as an oral diabetes treatment in humans. Two years later, in 1959, Aron Laboratories began selling it in France under the name Glucophage, which roughly translates to “glucose eater.”
Why the U.S. Waited 36 Years
If metformin worked well enough to sell in Europe by 1959, why did American patients have to wait until 1995? The answer comes down to a closely related drug called phenformin. Phenformin was another biguanide that hit the U.S. market earlier, and it caused severe lactic acidosis in some patients, sometimes fatally. The FDA pulled phenformin, and American physicians developed a deep distrust of the entire drug class.
That distrust extended to metformin, even though the two drugs behave quite differently at the molecular level. Getting past this required someone who could explain why metformin didn’t carry the same risks as what some researchers called its “evil twin.” Chemist Barbara Weil is credited with making this case to an FDA committee, using fundamental organic chemistry arguments to show that metformin’s structure made it far less likely to trigger the same dangerous buildup of lactic acid. Her persuasion worked, and the FDA approved Glucophage on March 3, 1995, with the application held by what is now EMD Serono Inc.
How Metformin Became a Top Prescription Drug
Once it reached the U.S. market, metformin’s rise was rapid. It quickly became the standard first-line treatment for type 2 diabetes, a position it still holds in clinical guidelines worldwide. By the most recent count, metformin ranks as the second most prescribed medication in the United States, with roughly 86 million prescriptions filled in 2023 alone. About 20 million individual patients received those prescriptions that year.
Its popularity comes from an unusual combination of strengths: it effectively lowers blood sugar, it doesn’t cause weight gain (and may even promote modest weight loss), it’s available as a cheap generic, and it has decades of real-world safety data behind it. Few diabetes drugs can claim all four.
Uses Beyond Diabetes
Over the years, doctors have prescribed metformin for conditions beyond type 2 diabetes, most notably polycystic ovary syndrome (PCOS). Metformin helps address the insulin resistance that drives many PCOS symptoms, though it remains officially unlicensed for this use in both adults and children. It’s one of the most widely used off-label medications in the world.
More recently, metformin has attracted attention for its potential effects on aging itself. Animal studies have shown it can delay biological aging, and the Targeting Aging with Metformin (TAME) trial, a planned six-year study across 14 U.S. research institutions involving over 3,000 participants aged 65 to 79, aims to test whether it can slow age-related decline in humans. The trial is still in the fundraising and planning stages through the American Federation for Aging Research.
The 2020 Recall and Current Safety
In 2020, multiple manufacturers voluntarily recalled certain extended-release metformin products after testing found they contained a probable carcinogen called NDMA above acceptable limits. The recalls affected brands from Apotex, Amneal, Lupin, Teva, and several others. Importantly, the recalls applied only to extended-release formulations, not the more commonly prescribed immediate-release tablets.
In response, the FDA now requires all companies manufacturing extended-release metformin to test every batch for NDMA contamination before releasing it to the U.S. market. Any batch that exceeds the acceptable intake limit cannot be sold. Standard immediate-release metformin was not affected by these recalls and remained continuously available throughout.
A Timeline at a Glance
- Medieval era: French lilac used as an herbal diabetes remedy in Europe
- Early 1800s: Guanidine isolated from the plant and tested as a synthetic compound
- 1957: Jean Sterne conducts the first human clinical trials of metformin in France
- 1959: Metformin goes on sale in France as Glucophage
- 1995: FDA approves metformin for the U.S. market on March 3
- 2020: Extended-release formulations recalled over NDMA contamination
- 2023: Metformin is the second most prescribed drug in the U.S., with 86 million annual prescriptions