Metformin for Cancer: Old Drug, New Uses

One of the world's most commonly prescribed medications for diabetes is the inexpensive but highly effective drug metformin. Derived from a herb called goat's rue (Galega officianalis), metformin works by suppressing the liver's release of glucose from its stores of glycogen. Metformin is not a cure for diabetes. Most type 2 diabetics have about three times the normal rate of production of glucose from glycogen from the liver. Metformin only reduces sugar release from the liver to about twice the normal rate. With diet and exercise, however, in many cases of early type 2 diabetes, metformin alone is enough to restore normal blood sugar levels. In more advanced type 2 diabetes, metformin is an important part of blood sugar control.

Metformin was synthesized in the 1920's, but the introduction of insulin therapy eclipsed its importance in early twentieth-century diabetes treatment. The usefulness of metformin in treating type 2 diabetes was not forgotten, and it was approved for use in France in the 1940's, the UK in the 1950's, in Canada in 1972, and the USA in 1995. Because the patents for generic metformin expired long ago and even the branded forms of the drug Glucophage and Glucophage-XR have been out for many years, metformin is extremely inexpensive, just $4 to $5 a month in the United States, and even less expensive in some other countries. Despite its extremely low cost and limited potential for drug company profits, researchers are constantly finding new applications for the drug.

What Is Metformin Good For?

Metformin isn't just used to treat type 2 diabetes. It is also used to prevent prediabetes from progressing to a fully diabetic condition. Because metformin doesn't act by increasing insulin production, it does not cause weight gain (it is usually accompanied by slight weight loss, although this is due to fluid shifts rather than fat burning). 

Because metformin increases insulin sensitivity, it is used to treat polycystic ovarian syndrome, a condition also known as PCOS. In PCOS, the ovaries are unable to stop receiving glucose from the bloodstream, and they react by overproducing testosterone. Metformin increases insulin sensitivity in other regions of a woman's body so that absorption of glucose is reduced in the ovaries, and hormonal imbalances are lessened.

Metformin is a potential anti-aging drug. It blocks a metabolic pathway known as mTOR, which regulates cell growth, cell reproduction, cell movement, and protein synthesis, all of which are critical in the development of cancer.

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What Kinds of Cancer May Respond to Metformin?

Metformin seems to be a potential therapy for endometrial (uterine) cancer. A woman's womb, like her ovaries, is unusually sensitive to glucose. Because it is essential for ovaries to continue to receive sugar from the bloodstream to protect a woman's eggs that have not been released yet, and it is essential for the uterus to receive sugar from the bloodstream when a woman is pregnant, these tissues do not develop insulin resistance the same way that other parts of a woman's body may. When other parts of the body become resistant to insulin, these tissues cannot stop receiving sugar.

Metformin For Cancers Of The Womb And Lung

Extra glucose does not necessarily cause endometrial cells to become cancer, but once they have developed cancer cell characteristics, it fuels their growth, proliferation, and escape to other tissues. More than almost any other kind of cancer, endometrial cancer is extremely sensitive to blood sugar levels. Women who are obese are at much high risk of endometrial cancer, not because being overweight causes cancer, but because the insulin resistance that raises blood sugar levels also locks fatty acids inside fat cells so that they cannot be released to be burned during exercise.

The progression of endometrial cancer is governed by several mechanisms, including the previously mentioned mTOR pathway. By blocking this route for protein synthesis, metformin helps reduce the production of proteins in individual cancer cells, reduces the reproduction of those cancer cells to form tumors, and helps keeps any tumors that form anchored in place so that they do not spread to other parts of the body. Cancer researchers are not using metformin as the only treatment for uterine cancer. Metformin is prescribed as an add-on treatment to another mTOR blocker, a drug called everolimus, in addition to estrogen blockers such as letrozole. Adding metformin to the mix allows other cancer drugs to be used in lower doses, with fewer side effects, and in early test results extends life in advanced uterine cancer. In the near future, metformin will be tested as a treatment for the early stages of uterine cancer.

Metformin For Lung Cancer

Metformin is being used in a different way for treating inoperable non-small cell lung cancer. Non-small lung cancers carry a dismal prognosis, especially when they occur in locations in which their removal would compromise lung function. Just about the only treatment for this kind of lung cancer is radiation.

Metformin does not have a direct effect on the cancer itself, but it makes lung cells more susceptible to radiation. Giving metformin may make treatment possible with lower doses of radiation that cause fewer side effects, extending life with greater comfort. 

Reducing the Side Effects of Cis-Platin

Metformin is also used in the treatment of small-cell lung cancer to reduce the side effects of cis-platin, the chemotherapy drug also known as Platinol. One of the more troubling problems in Platinol treatment is the stinging, burning, numbness, and increased risk of infection caused by peripheral neuropathy, damage to nerves caused by the drug. Metformin reduces the symptoms of neuropathy, helping to preserve the ability to walk and to use the hands without pain. This application is still considered investigational, but if you are receiving cis-platin from lung cancer it won't hurt to ask your physician if metformin would help you.

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Is there any downside to using metformin?

Metformin 850's sometimes cause stomach upset and runny bowel movements, but this is not a common problem with the smaller metformin 500's. In very, very rare instances use of metformin can trigger a condition called lactic acidosis, but this is primarily a problem in patients who are experiencing renal failure. Simple blood tests can confirm that the kidneys are healthy enough for use of the drug.

The good things about metformin are that it is extraordinarily safe, and extraordinarily inexpensive. Look for it to become more and more common in cancer treatment.