Metformin

Authors

Laura Pole, RN, MSN, OCNS, BCCT Senior Researcher

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Nancy Hepp, MS, BCCT Project Manager

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Last updated September 24, 2021.

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

  • Before using this therapy, consult your oncology team about interactions with other treatments and therapies. Also make sure this therapy is safe for use with any other medical conditions you may have.
  • Metformin is a prescription drug used to control high blood glucose in type 2 diabetes.
  • BCCT is interested in metformin because reduced risk of cancer and anticancer effects in several cancers, especially in diabetics, is demonstrated in lab, animal and human studies.
  • Most of the evidence on metformin's uses related to cancer comes from epidemiological, observational and case-control studies.
  • Many clinical trials are in progress to test metformin’s effects in preventing cancer and in supplementing other cancer treatments.
  • 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 a supplement to cancer treatment.

Metformin is a prescription drug used to control high blood glucose in 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 cancer treatment. Off-label use is a drug’s application for a disease or condition that has not yet received FDA approval. 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

Highlighted Videos

Donald Abrams, MD, explains how metformin can be used as a cancer therapy in a 2014 presentation.

BCCT advisor Brian Bouch, MD, explores metformin for cancer care in this interview from 2018.

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 and are described below. 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. See also preliminary indications that metformin may interfere with chemoradiotherapy in Cautions below.

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-diabetes treatment. However, diabetics on metformin have shown 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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Brain and Nervous System Cancers

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Breast Cancer

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Cervical Cancer

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Colorectal Cancer

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Kidney Cancer

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Liver Cancer

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Lung Cancer

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Lymphoma

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Multiple Myeloma

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Ovarian Cancer

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Pancreatic Cancer

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Prostate Cancer

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Uterine/Endometrial 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

Clinical Evidence

Animal Evidence

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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.

Cancer in General

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Breast Cancer

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Colorectal Cancer

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Liver Cancer

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Lung Cancer

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Pancreatic Cancer

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Prostate Cancer

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Uterine Cancers (Endometrial and Sarcoma)

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Lab and Animal Evidence

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Optimizing Your Terrain

Creating an environment within your body that does not support cancer development, growth or spread

  • Anti-inflammatory108
  • Reduced blood glucose (glycemia);109 elevated levels are a risk factor for colorectal cancer110 and are associated with poorer survival in some reports111
  • Reduced levels of insulin, fasting glucose, CRP, HOMA, leptin, BMI, and Ki-67 in breast cancer patients receiving metformin as treatment for diabetes112
  • Increased phosphorylation of AMPKα113
  • Physical activity and metformin both led to weight loss as well as significant changes in insulin and other biomarkers in colorectal cancer and breast cancer survivors.114  
  • Decrease in insulin resistance and metabolic syndrome related to androgen deprivation therapy in men without diabetes who received metformin and made lifestyle changes.115
  • Did not affect expression of markers of the PI3K–Akt–mTOR or insulin signaling pathways, and did not result in weight loss among women with atypical hyperplasia or endometrioid endometrial cancer116

Access

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

Cautions

Cautions Specific to Cancer Treatments and Outcomes

  • A small study of people without diabetes who have locally advanced non–small cell lung cancer found that use of metformin during chemoradiotherapy was linked to worse treatment efficacy and increased toxic effects compared to chemoradiotherapy alone. The proportion of patients who experienced a failure event within one year (locoregional disease progression, distant metastases, death, or withdrawal) was 69.2% in the metformin arm versus 42.9% in the control arm.117
  • Gastrointestinal toxicity is noted for prostate cancer patients receiving abiraterone therapy in a small study.118
  • A 2012 study 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.119 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.”120121

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.128

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.129

Dosage information and recommendations are available from these sources:

Integrative Programs, Protocols and Medical Systems

For more information about programs and protocols, see our Integrative Programs and Protocols page.

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.133

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..134

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.”135

From a 2013 presentation by integrative oncologist and BCCT advisor Dwight McKee, MD: “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.”136

Avoiding sugar and taking other measures to curb insulin resistance can achieve some of the same impacts without the side effects of metformin.

Barry Elson, MD

From a 2009 book by integrative oncologist and BCCT advisor Keith Block, MD: 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.”137

Integrative physician and BCCT advisor Barry Elson, MD, February 18, 2021: Observational studies find benefit in those with insulin resistance and/or obesity, perhaps because metformin stimulates the tumor suppressor AMPK. AMPK is poorly activated in obese patients, since they are generally deficient in adiponectin, an AMPK-activating hormone.

In addition to chemical stimulation of AMPK, avoiding sugar and taking other measures to curb insulin resistance can achieve some of the same impacts without the side effects of metformin. Several excellent natural remedies are available, such as these:

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 syndrome138
  • Non-alchoholic fatty liver disease139
  • Weight loss140

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

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