The History of the Diabetes Drug Metformin

Sometimes it takes a long time for a drug to reach patients. If you have prediabetes, consider medication. Here's what you should know about metformin.

For decades metformin, the leading medication for type 2 diabetes, was neglected and even banned. Its story teaches two lessons: How scientists can turn a promising plant into a useful drug and the sometimes long, slow path to acceptance.

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The history of metformin

During medieval times, people ate the plant Galega officinalis, also known as Goat’s rue, French lilac, or Italian fitch, to relieve frequent urination, one symptom of diabetes. It has a long history as a folk remedy, though it can also be toxic, particularly to livestock. When scientists discovered that one of the chemicals it contained lowered blood sugar levels, they looked for safer variations. 

Just before World War I, researchers in Paris identified a key chemical, other scientists in Edinburgh chipped in, and, in 1922, researchers in Dublin synthesized metformin, or dimethyl biguanide. The new form was safe and easier on the digestive track than earlier compounds. Starting with a low dose and increasing slowly also helped minimize gastrointestinal side effects. But around the same time, insulin stole the stage as a diabetes treatment. 

By the late 1950s, metformin had been named “Glucophage,” which means “glucose eater.” Around the same time, an American group discovered phenformin, or phenylethyl biguanide. Ciba-Geigy marketed it around the world, although reports emerged that it could cause a condition called lactic acidosis and lead to deaths. A small French company manufactured metformin, which became popular only in France and Scotland. 

In the 1970s, the evidence that phenformin posed a fatal risk of lactic acidosis mounted and, in 1977, it was banned in the United States and elsewhere. Some countries put restrictions on metformin as well.

Your liver metabolizes phenformin, and the drug accumulates in patients with a genetic deficiency of a particular enzyme. Metformin is excreted in urine. It has been tied to lactic acidosis in overdoses or in people with advanced renal failure, but it is generally safe.

In France and Scotland, endocrinologists were getting good results with metformin, and they continued to prescribe it widely. 

Research continued to show that metformin, used correctly, was safe and effective. Still, Americans didn’t get the benefit of metformin until the mid-90s. 

In 2012, the American Diabetes Association and its European counterpart declared that metformin should be the first-choice treatment for obese people with type 2 diabetes. It is also used to treat polycystic ovary syndrome and gestational diabetes.

The drug improves the way your body handles insulin, thereby lowering your blood glucose. It is usually prescribed when diet and exercise aren’t enough to lower your blood sugar.

You will usually need to take metformin your entire life. It is possible to stop taking the drug if lifestyle changes put your diabetes into remission.

Interestingly, people who take metformin seem to have lower rates of pancreas, colon, thyroid, breast, and prostate cancers, and researchers are hot on the trail to use metformin for cancer prevention.

Should you take metformin if you don’t have diabetes? 

The debate continues about whether metformin should be prescribed to prevent diabetes. The main recommendation for prevention is eating better, losing weight, and exercising. In 2008, a panel for the American Diabetes Association concluded that doctors should also consider metformin for patients who are severely obese and for those with prediabetes — blood sugar above normal but not yet in the diabetes range.

In a study of more than 3,200 people with prediabetes, researchers created three groups:

• The control group, put on a placebo
• A group that received 850 mg of metformin twice daily
• Another group assigned to a program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week

Over the next three years or so, the weight-loss program lowered the chance of developing diabetes by 58 percent and needing metformin by 31 percent.

In real life, there’s no reason why you can’t take metformin and work on your exercise program and food portion sizes. Some evidence suggests that metformin may be even more effective if you are younger than 60 or have a BMI greater than 35. If you do nothing, there’s a good chance you’ll never develop diabetes. But if you’re in the unlucky group, diabetes tends to arrive within three to eight years.

Your doctor may not have mentioned the drug to you, however. In one study with a national sample of more than 17,000 working-age adults, researchers discovered that doctors offered metformin to only 3.7 percent of patients with prediabetes.

“Our findings indicate that metformin is rarely prescribed for diabetes prevention despite a strong evidence base in the literature for more than 10 years and inclusion in practice guidelines for more than 6 years,” wrote the authors, led by Tannaz Moin, MD, of the University of California, Los Angeles.

Who should be tested for diabetes or pre-diabetes?

Doctors should test adults who are overweight or obese and over the age of 45, and any overweight person who has an additional risk factor for prediabetes and type 2 diabetes.

Risk factors include:

• Inactivity
• A parent, brother, or sister with diabetes
• Giving birth to a baby weighing more than 9 pounds
• High blood pressure
• Low “good” cholesterol or high triglycerides
• Polycystic ovary syndrome
• A history of heart disease

There is a caveat, however. People with an underactive thyroid may aggravate that problem with metformin, some research shows.

If your doctor hasn’t suggested metformin to treat your prediabetes, ask why. The answer may be that you’d be better off losing weight and getting more exercise.

But taking medication can sometimes get you to focus on a problem. Evaluate for yourself whether taking metformin will sap or enhance your motivation to change your ways. Develop a clear strategy to lower your diabetes risk that includes every resource available to you, which might be a gym buddy or joining a weight-loss group. 

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