Metformin

Also known by these names

Brand names:

  • Fortamet
  • Glumetza
  • Glucophage
  • Glucophage XR
  • Riomet

Evidence shows that metformin may reduce risks of some types of cancer and also may improve outcomes in people with certain cancers, especially with people with diabetes.

Key Points

  • Metformin is a prescription drug used to control high blood glucose in type 2 diabetes.
  • BCCT is interested in metformin because lab, animal and human studies demonstrate reduced risk of cancer and anticancer effects of metformin in several cancers, especially in diabetics. Furthermore, metformin has low toxicity, is inexpensive, is very familiar to allopathic physicians and is widely available.
  • Most of the evidence of cancer-related use of metformin comes from epidemiological, observational and case-control studies.
  • Many clinical trials are in progress to test the cancer-preventive and adjuvant cancer treatment effects of metformin in humans.
  • Metformin has low toxicity and is inexpensive, widely available and very familiar to most physicians.
  • Although generally safe, there are cautions, side effects, contraindications and drug interactions with metformin. Metformin should be used only under medical supervision.
  • Some integrative cancer care physicians use metformin off-label as an adjunct to cancer treatment.

Metformin is a prescription drug used to control high blood glucose with type 2 diabetes. Evidence shows that metformin may reduce risks of some types of cancer and also may improve outcomes in people with certain cancers, especially with people with diabetes. Some integrative cancer care physicians use metformin off-label—for a disease or condition that has not yet received US Food and Drug Administration (FDA) approval—for cancer treatment. Every US state allows drugs to be used off-label as long as enough evidence supports its use.

“Results of numerous clinical studies, although inconclusive, indicate that metformin use, and possibly cumulative duration of therapy and cumulative dose, is associated not only with decreased incidence of cancer in the diabetic population, but also with the better outcome in cancer patients. . .Definite data on the efficacy of metformin as neoadjuvant therapy in cancer patients is lacking.”1

Treating the Cancer

Working against cancer growth or spread, improving survival, or working with other treatments or therapies to improve their anticancer action

Clinical Evidence

Clinical trials using metformin as a cancer adjuvant (supplement) to cancer treatment are in progress, as described here. Most of the evidence in humans to date is from observational, population cohort and case-control studies. Evidence from these types of studies is not strong enough to conclude that metformin is the cause of the positive effects seen.

How It Works

Diabetes and Cancer

Evidence shows these intriguing relationships between diabetes and cancer:

  • People with diabetes show a higher incidence of certain types of cancer, such as colorectal, liver, pancreatic, endometrial, breast and bladder cancers.2
  • Postmenopausal women with diabetes are at higher risk for invasive cancer in general, as well as cancers of the colon, liver, pancreas and endometrium and non-Hodgkins lymphoma.3
  • Type 2 diabetes is associated with a poorer prognosis in people with cancer, depending on the cancer type and anti-diabetic treatment. However, diabetics on metformin have showed improved survival compared with other treatments for diabetes and in comparison with a nondiabetic population.”4

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Cancers in General

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Breast Cancer

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Colorectal Cancer

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Glioblastoma

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Liver Cancer

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Ovarian/Endometrial Cancer

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Prostate Cancer

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Lab and Animal Evidence

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Managing Side Effects and Promoting Wellness

Managing or relieving side effects or symptoms, reducing treatment toxicity, supporting quality of life or promoting general well-being

Animal Evidence

Peripheral Neuropathy

A preclinical study showed that mice who were given metformin along with the chemotherapy drug cisplatin (compared with placebo and cisplatin) had significantly less loss of paw sensitivity and protected peripheral-nerve endings.32 An article in late 2014 described a study in progress at MD Anderson’s Department of Symptom Research investigating whether metformin relieves chemotherapy-induced peripheral neuropathy.

Cognitive Impairment

In a 2016 animal study, researchers found that cognitive impairment due to the chemotherapy drug cisplatin is prevented by treatment with metformin prior to cisplatin treatment.33

Reducing Risk

Reducing the risk of developing cancer or the risk of recurrence

Clinical Evidence

Clinical trials using metformin as a cancer preventive are in progress

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Access

Metformin is available with a prescription in oral form at pharmacies.

Cautions

A 2012 study by Mazzone et al. found that diabetics who developed lung cancer while receiving metformin were more likely to present with metastatic disease, had reduced survival, and had a different histology distribution (microscopic tissue characteristics) than those who were not receiving metformin.44

However, Yin et al. provided context that “the study by Mazzone et al. is the only study showing a significantly increased risk for death associated with metformin treatment whereas most of the studies in our data pool . . . favor a protective effect of metformin.”45

Common Side Effects/Adverse Events

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Precautions

Numerous precautions are involved in taking metformin, and patients must notify their doctors of certain conditions that will increase their risk of developing serious problems from taking metformin. For a listing of these precautions, see: WebMD: Metformin HCL: Precautions.

Metformin is not recommended in patients with abnormal renal or hepatic function, nor should it be prescribed in patients with heart failure.48

Interactions

Numerous potential drug interactions are associated with metformin. Consult with your pharmacist for interactions, and discuss using metformin with your doctor. For a listing of these interactions see WebMD: Metformin HCL: Interactions.

Dosing

BCCT does not recommend therapies or doses, but only provides information for patients and providers to consider as part of a complete treatment plan. Patients should discuss therapies with their physicians, as contraindications, interactions and side effects must be evaluated.

“Most of the cancer clinical trials of metformin use the same doses typically used to treat diabetes.” These are typically trials of cancer prevention. Some suggest higher doses may be more effective in the adjuvant cancer treatment setting, but safety and effectiveness of higher doses has not yet been established in clinical trials.49

Dosage information and recommendations are available from these sources:

Integrative Plans, Protocols and Medical Systems

For more information about plans and protocols, see our Integrative Plans and Protocols page.
  • Plans, protocols and programs
    • Block program50
      • Pharmaceutical glycemia terrain modifier
    • Chang strategies51
    • McKinney protocols52
      • Breast cancer
      • Carcinoid/neuroendocrine cancer
      • Lymphoma
      • Melanoma
      • Pancreatic cancer
      • Prostate cancer
      • Sarcoma
      • Thyroid cancer

Commentary

We found that metformin was associated with benefit regardless of cancer treatments.

Margel et al.

From a 2013 article by Margel et al: “There are several clinical implications of our findings. First, consistent with current guidelines, metformin should be considered first-line therapy among patients with prostate cancer and diabetes, not only for diabetes control but possibly to improve cancer prognosis. Second, we found that metformin was associated with benefit regardless of cancer treatments. These results suggest that metformin may further improve survival as an adjunct therapy, even among those already receiving optimal cancer treatments. Finally, metformin may be ideal for secondary prevention because it is inexpensive, safe, and well tolerated.53

Our results suggest that metformin is the drug of choice in the treatment of patients with cancer and concurrent type 2 diabetes.

Yin et al.

From a 2013 article by Yin et al.: “Patients with type 2 diabetes have increased cancer risk and cancer-related mortality, which can be reduced by metformin treatment. However, it is unclear whether metformin can also modulate clinical outcomes in patients with cancer and concurrent type 2 diabetes. Our meta-analysis provided evidence that there was a relative survival benefit associated with metformin treatment compared with treatment with other glucose-lowering medications. Our results suggest that metformin is the drug of choice in the treatment of patients with cancer and concurrent type 2 diabetes..54

From a 2014 article by Yu et al: Any conclusions without a large-scale prospective randomized study should be cautious. However, “considering the high prevalence of prostate cancer in Western countries and its rising incidence in the world, [and} the low cost and favorable toxicity of metformin, the applicability of metformin use as recommendation for prevention or treatment of prostate cancer may suit multiple populations, in people both with or without type 2 diabetes, and in both developed or developing countries.”55

From a 2013 presentation by Dwight McKee: “Metformin can be safely given as an off-label adjunctive treatment in cancer patients, especially breast, ovarian, colorectal, prostate, pancreas and perhaps in glioma patients who have type 2 diabetes, metabolic syndrome, elevated circulating insulin levels, or are obese, or even simply those who cannot or do not adhere to a low-carb, low-fat diet.”56

From a 2009 book by Keith Block: If you are taking glycemic support supplements or terrain modifiers and they are not correcting your glycemic imbalance, Keith Block, MD, suggests talking with your physician about increasing the doses of these, and/or considering using metformin. “Metformin . . . is approved for insulin resistance, reduces the liver’s ability to release glucose and so may be helpful for patients whose glucose imbalance results from this mechanism.”57

Non-cancer Uses of Metformin

BCCT has not reviewed the effectiveness of this therapy for non-cancer uses. Besides diabetes, metformin has been investigated with these conditions:

  • Polycystic ovary syndrome58
  • Non-alchoholic fatty liver disease59

BCCT has not reviewed the effectiveness of this therapy for non-cancer uses.

Written by Laura Pole, RN, MSN, OCNS; and reviewed by Nancy Hepp, MS; most recent update on January 14, 2019.

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