Metformin is known as a drug for type 2 diabetes, so some might find it surprising that it is mentioned on a cancer website. In diabetes, metformin decreases glucose production by the liver, decreases the absorption of glucose in the intestines, and improves insulin resistance of the cells. Interestingly, metformin began to garner attention in cancer when a study found that diabetics on metformin have lower cancer rates than diabetics not on metformin. That was big news at the time, because diabetics are known to have higher rates of pancreatic, liver, colon, breast, bladder, uterine, and rectal cancers compared to non-diabetics.
Where does metformin come from?
Metformin was derived from the French lilac (Galega officinalis), after it had been shown that this herb lowered blood sugar. The generic form is known as glucophage, meaning “sugar eating.”
How metformin works
Metformin has been used as the first-line drug for diabetes in the United States for the past 20 years, and it has the advantage of lowering blood sugar levels safely without the risk of hypoglycemia (blood sugar which is too low). On a basic level, it makes sense that metformin reduces cancer cell growth and development. Because we know that cancer cells love sugar, a drug which helps the body reduce blood sugar levels should also prevent cancer from having as much food for growth. However, research into how metformin works on cancer cells suggests that it also inhibits what is called the mTOR pathway. The mTOR pathway is crucial to cancer cells acquiring energy, growing, and spreading.
Metformin also reduces circulating levels of insulin (which is needed for cells to take up glucose), as well as insulin-like growth factor 1 (IGF-1). We know that both insulin and IGF-1 play a role in cancer cells acquiring energy, so reducing both of these also seems to be important in starving cancer cells.
Metformin as an antioxidant
An additional benefit of metformin is that it works as an antioxidant. As a result, it scavenges for what are called reactive oxygen species, abbreviated ROS, which are produced when cells burn sugar for energy (this is one of many reasons why I recommend my eating plan, which is based on using fat for energy rather than carbohydrates). In a high sugar environment, numerous ROS are created and this causes significant damage to cells. This causes oxidation, which is a rusting of the cell membrane. The cell membrane damage that results prevents cells from working well, allows more toxins to enter the cell, and ultimately changes the way the cell functions. DNA damage results, and cells are on their way to becoming cancerous.
Metformin mimics caloric restriction
Caloric restriction is the only strategy which has been shown to truly reverse the effects of aging. We know that restricting calories results in lower rates of cancer, as well as improved outcomes in patients who are undergoing cancer treatment. Metformin mimics caloric restriction in lab studies, meaning that it makes the body’s cells think that calories are being restricted even if they are not. Intermittent fasting does the same thing, which is one reason why I recommend it for everyone (and especially cancer patients).
How metformin is used in cancer treatment
Dr. Stegall frequently uses metformin for cancer treatment as an off-label drug. Off-label means that metformin was not approved for cancer treatment, but is used in specific cases due to its suspected mechanism of action, its good safety profile, and its results in lab studies. It also has the benefit of being very affordable in its generic form, glucophage. Dr. Stegall prefers glucophage XR, taken once daily, as the extended release tends to be better tolerated and more convenient than the twice daily dosage form.