This fascinating compound was discovered nearly a century ago. Scientists realized that it could lower blood sugar in an animal model (rabbits) as early as 1929 but it wasn’t until the late 1950s that a French researcher came up with the name Glucophage (roughly translated as glucose eater). The FDA gave Glucophage (metformin) the green light for the treatment of type 2 diabetes in 1994, 36 years after it had been approved for this use in Britain.
Glucophage lost its patent protection in the U.S. in 2002 and now most prescriptions are filled with generic metformin. This drug is recognized as a first line treatment to control blood sugar by improving the cells’ response to insulin and reducing the amount of sugar that the liver makes. Unlike some other oral diabetes drugs, it doesn’t lead to weight gain and may even help people get their weight under control.
Starting early in 2000, sales of metformin were challenged by a new class of diabetes drugs. First Avandia and then Actos tested metformin for leadership in diabetes treatment. Then Avandia lost its luster because of a link to heart attacks and strokes and now sales are miniscule because of tight FDA regulations. Actos is coming under increasing scrutiny as well. The drug has been banned in France and Germany because of a link to bladder cancer. The FDA has also required Actos to carry its strictest black box warning about an increased risk of congestive heart failure brought on by the drug.
This all means that metformin has regained its reputation as the best bang for the buck when it comes to type 2 diabetes management. The American College of Physicians has recommended metformin as the first line of treatment when lifestyle changes (diet, exercise and weight loss) have not led to adequate blood glucose control. That may be why nearly 50 million metformin prescriptions were dispensed last year.
Despite all the warm, fuzzy feelings about metformin for type 2 diabetes, there are some caveats. This drug does cause a number of side effects, especially when it comes to the gastrointestinal tract. They can be especially bothersome during the first few weeks of treatment. After several weeks, however, the digestive symptoms may fade away. If they recur, however, notify your doctor immediately as they could be symptoms of lactic acidosis (see below). Here is a list of adverse reactions to watch out for:
METFORMIN SIDE EFFECTS
- Stomach ache
- Loss of appetite
- Lactic acidosis (symptoms may include irregular heart rate, nausea, stomach pain, lethargy, anxiety, low blood pressure and rapid heart rate) Notify your physician immediately if you notice any of these symptoms!
These side effects may seem daunting, but most people tolerate metformin quite well. The drug can be dangerous for people with kidney disease, however. They should not take the drug, and everyone on metformin should have their kidney function monitored regularly (at least once a year). People with congestive heart failure should not take metformin either.
There is an unexpected bonus to metformin therapy. There is growing evidence that this drug has an anti-cancer effect that may both prevent cancers from developing and spreading. In particular there are data suggesting that metformin may lower the risk of developing breast cancer, liver cancer, pancreatic cancer and colorectal cancer in people with diabetes and that the overall risk of developing cancer in such patients is substantially lower. More about this below.
A final word of caution, though. There are some nutritional consequences of metformin therapy. Here are some stories from readers. Please add your own comments about metformin treatment below theirs.
Q. I have read that metformin can cause a deficiency of Vitamin B12. I have not been able to find again the source of this information and would like your input.
A. This is from the prescribing information at DailyMed, identical to what is published in the PDR:
“Vitamin B12 Levels: In controlled clinical trials of metformin of 29 weeks duration, a decrease to subnormal levels of previously normal serum Vitamin B12 levels, without clinical manifestations, was observed in approximately 7% of patients. Such decrease, possibly due to interference with B12 absorption from the B12-intrinsic factor complex, is, however, very rarely associated with anemia and appears to be rapidly reversible with discontinuation of metformin or Vitamin B12 supplementation. Measurement of hematologic parameters on an annual basis is advised in patients on metformin and any apparent abnormalities should be appropriately investigated and managed (see PRECAUTIONS: Laboratory Tests). Certain individuals (those with inadequate Vitamin B12 or calcium intake or absorption) appear to be predisposed to developing subnormal Vitamin B12 levels. In these patients, routine serum Vitamin B12 measurements at two- to three-year intervals may be useful.”
Q. My husband took metformin for years with no known side effects. Then his kidney functions started to deteriorate so he was seen by a specialist who immediately took him off metformin. He said that drug was very hard on kidneys and anyone who had any variations in kidney functions should not be taking it.
A. As mentioned above, kidney function must be monitored regularly to prevent just such a complication.
Q. I am suffering from such severe diarrhea I am sometimes afraid to leave the house. I also have bad gas and bouts of abdominal pain. I suspect the metformin I take for diabetes, but my doctor says my symptoms are not from my medicine.
The Prevacid I take for my heartburn isn’t helping enough to justify the expense. I am also experiencing pain and tingling in my toes.
A. Metformin (Glucophage) can cause diarrhea, nausea, heartburn, flatulence and stomachache. Acid-suppressing drugs like lansoprazole (Prevacid), omeprazole (Prilosec) or esomeprazole (Nexium) won’t solve the problem completely and may interfere with absorption of vitamin B12.
Metformin is also linked to reduced levels of vitamin B12. Because this vitamin is crucial for nerve function, deficiency can contribute to numbness, tingling or pain of the toes, feet or fingers, trouble walking, memory problems, depression, confusion and burning tongue.
The Miracle of Metformin
Before you give up on metformin because of side effects and scary stories, we want to tell you about some surprising benefits of this drug. There is growing evidence that metformin may have impressive anti-cancer activity. Not only does the drug seem to reduce the risk of developing a number of common cancers but it might reduce the spread of cancer once it is diagnosed.
Researchers are beginning to tease out one of the proposed mechanisms for the anti-tumor action of metformin, especially in prostate cancer. A study in the journal Prostate Cancer and Prostatic Diseases (Jul. 28, 2015) reported that effective treatment for aggressive or advanced disease is challenging. The researchers note:
“One potential target is the cancer stem cell (CSC). CSCs have been described in several solid tumors, including prostate cancer, and contribute to therapeutic resistance and tumor recurrence. Metformin, a common oral biguanide used to treat type 2 diabetes, has been demonstrated to have anti-neoplastic effects. Specifically, metformin targets CSCs in breast cancer, pancreatic cancer, glioblastoma and colon cancer.”
By exploiting a metabolic weakness in cancer stem cells, metformin theoretically makes these problem cells more vulnerable to conventional cancer therapies and could reduce the likelihood of cancer resistance and recurrence.
The Bottom Line
Metformin is an old diabetes drug that is being rediscovered for its potential role against cancer. Only time will tell whether it will live up to initial expectations. In the meantime, metformin remains one of the least expensive prescription drugs in the pharmacy. As long as people are vigilant about side effects and complications it could become one of the most intriguing drugs on pharmacy shelves. Here is a link to our article “Is Metformin a Modern Miracle Medicine?“