Metformin is a medication derived from the herb Galega officinalis (French lilac, also known as Goat’s Rue or Italian Fitch) and has been used as a traditional botanical (tea infusion) for over 3,000 years to relieve polyuria (frequent urination) and halitosis (sweet odor on the breath), both are now well known symptoms of diabetes. Approved for the treatment of hyperglycemia in Britain since the late 1950’s, Canada in the 1970’s and U.S. in 1995, metformin is the most widely prescribed diabetes drugs (over 120 million prescriptions filled yearly worldwide).
Although the mechanism of action of metformin in diabetes is only partially understood, metformin treatment reduces levels of both blood glucose and insulin. The primary mechanism of action in diabetes is on the liver through reduced production of glucose. (ref)
Scientists have recognized for years that certain cancers (i.e. breast, prostate, colon, endometrial, pancreatic, lung, etc.) thrive in the presence of elevated blood sugar and insulin levels, eventually leading to higher rates of tumor development, progression and metastases. By keeping blood sugar levels low (either by diet or medications), cancer development and progression is impaired. (I have written more extensively about the role of sugar and insulin in cancer development and progression on the IOE website.)
Anti-cancer effects of metformin:
Over the last decade, numerous studies have discovered that metformin (compared with other glucose-lowering therapies) appears to have powerful anti-cancer effects that extend far beyond simply lowering blood sugar and insulin: (ref)
- activation of AMP-kinase (AMPK):suppression of human epidermal growth factor receptor-2 (HER-2)
- AMPK inhibits glucose production in the liver (indirectly reducing insulin and insulin-like growth factor, IGF-1, levels)
- AMPK increases insulin sensitivity (reducing blood sugar levels) by increasing glucose uptake in muscle
- AMPK activation blocks gene expression of cancer promoting proteins, leading to inhibition of tumor cell growth (induction of cell cycle arrest and apoptosis)
- AMPK inhibits the genetic signaling of the molecular complex, mTOR (mTOR activation is implicated in cancer development and chemotherapy resistance)
- selective killing of cancer stem cells (often chemotherapy resistant cells)
- aromatase inhibition (decreasing estrogen production in the body)
- increases the effectiveness of chemotherapy (higher pathologic complete response) and radiation therapy (radiation sensitization)
- significantly decreases body mass index (via effects of maintaining lower blood sugar levels and appetite suppression); obesity increases systemic inflammation, estrogen levels, free radicals (all of which can stimulate cancer growth and progression)
- lower blood sugar levels maintain lower insulin secretion (insulin and its’ associated hormone, IGF-1, are tumor growth factors)
Metformin & breast cancer:
- 56% reduction in the risk of developing breast cancer among those taking metformin versus not taking metformin (ref)
- 24% of diabetics breast cancer patients taking chemotherapy with metformin had a complete remission versus 8% who were not taking metformin (ref)
- 42% reduction in precancerous tissue changes among those individuals taking metformin for 1-month versus no change among matched controls not on metformin (ref)
- 24-45% improved progression free survival and 35% improved overall survival among type-2 diabetics treated with chemotherapy and metformin for non-small cell lung cancer versus those who were treated with chemotherapy without metformin (ref)
- 44% reduction in the risk of developing prostate cancer among those taking metformin versus those not taking metformin (ref)
- 62% reduction in the risk of developing pancreatic cancer among those taking metformin versus those not taking metformin (ref)
Ongoing clinical trials of metformin and cancer:
Currently, a number of clinical trials examining the use of metformin as a cancer therapy are underway including studies in prostate, breast, endometrial and pancreatic cancer patients. Increasingly, published data support the anti-cancer effects of metformin not only in diabetics but also among those without diabetes. Therefore, many of these clinical trials are enrolling cancer patients with or without diabetes. One of the largest studies was recently initiated by the National Cancer Institute of Canada Clinical Trials Group (NCIC MA.32) examining the effect of metformin versus placebo in over 3,500 non-diabetic women with early stage breast cancer. These clinical trials will be integral to the development and effective use of metformin as an anticancer therapy.
Metformin dosage and contraindications:
The typical metformin dosages are 250-850 mg taken 2-3 times each day (before meals).
Read more about the contraindications for metformin here.
Metformin is a promising anti-cancer therapy with multiple mechanisms of action that extend beyond its classical role as an anti-diabetes agent. As one of the most widely prescribed, well-studied, safe and inexpensive (generics have been available for years) medications on the market, metformin stands a good chance of becoming one of the standard adjuvant therapeutic agents in our war against cancer development, progression and recurrence.