Metformin, a prescription drug used to manage diabetes, has shown some benefits in lower risks of cancer and better survival, mostly among people with diabetes or high blood sugar.

How can metformin help you? What the research says

We summarize the clinical evidence for each medical benefit here. We begin with our assessment of the strength of evidence within each category, followed by a brief summary of individual studies or reviews of several studies. In assessing the strength of evidence, we consider the study design, number of participants, and the size of the treatment effect (how much outcomes changed with treatment).

To see more details, click the plus sign to the right of any section.

Commentary on research methodology

CancerChoices Lead Researcher Nancy Hepp and Research Associate Andy Jackson, ND: Trying to make sense of the research evidence regarding metformin’s effects on cancer incidence and outcomes is fraught with obstacles. Far too many studies do not report whether the study population includes people without diabetes. This makes a huge difference in interpreting the study findings, as people with diabetes have a much higher risk of cancer and of worse outcomes after a cancer diagnosis. See Blood sugar and insulin resistance › 

Some examples of how different comparisons can change interpretations of data:

Example 1: People with diabetes treated with metformin are compared to people without diabetes in terms of cancer incidence or survival in an observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study. No difference is found and the researchers conclude that metformin provides no benefit. 

This is a little bit like studying people who have a special booster device for running speed. The people with the device start 100 yards back from the starting line in a race, but they cross the finish line at the same time as people starting at the starting line. The researchers conclude that the special device doesn’t improve running speed because everyone finishes at the same time. 

People with diabetes would be expected to have higher incidence and worse survival for some types of cancer compared to people without diabetes. Finding that people with diabetes have similar results to people without diabetes may be evidence that metformin is associated with improved outcomes among people with diabetes, but this is reported as “no evidence of an effect.” Some studies don’t adjust their data or even mention the different starting points for people with diabetes compared to people without diabetes. 

Since a huge majority of people treated with metformin in observational studies have diabetes, a comparison simply of metformin vs no metformin without accounting for diabetes is not an appropriate comparison. A better comparison is between people with diabetes treated with metformin compared to people with diabetes not treated with metformin. Some of the very large observational studies do not make this comparison. In our summaries, we give as much detail about the diabetes status of study participants as the researchers provide, but too often we’re left wondering. 

Designing a study observing the effects of metformin compared to a placebo on cancer outcomes among people with diabetes would be difficult. Ethical issues would arise, as withholding diabetes treatment from people who need it would lead to ethical and likely medical issues that could negatively affect the patients as well as the study outcomes. Studies comparing cancer outcomes among people treated with metformin compared to other diabetes treatments are available, but the interpretation of the comparison is not as clean as with a placebo. Some studies compare metformin to one or two specific diabetes drugs, while other studies lump all the other diabetes treatments together. Comparing across studies is difficult, as which specific drugs are used as the comparison makes a big difference in interpretation.

In this review as we grouped studies into 1) those limited to people with diabetes and 2) those comparing people with diabetes treated with metformin to people without diabetes, we found highly reliable differences in outcomes across cancer types. Metformin consistently shows benefits for cancer risk and survival among people with diabetes, but not much benefit among people without diabetes. Data on specific cancer types can vary, and more research is needed.

However, even just among people with diabetes, the study design may still be building in a complication (or confound, as researchers term it). People who are treated with metformin tend to have less advanced or less complicated diabetes. When metformin is no longer sufficient to provide blood sugar control, people are often switched to other treatments. Unless studies look specifically at people’s levels of blood sugar and/or insulin resistancea condition in which cells in your muscles, fat, and liver don’t respond well to insulin and can’t efficiently take up glucose from your blood for energy, they may be comparing the people with more advanced diabetes (not using metformin) to people with less advanced diabetes (using metformin). We would expect higher risk of cancer and worse survival among people with more advanced diabetes, and therefore comparatively better survival and lower risk among people with less advanced disease, who coincidentally are the people treated with metformin. The reason for the difference may not be the use of metformin, but the status of blood sugar control and insulin resistance. We found few studies controlling for this confound.

Example 2: People with cancer without a diabetes diagnosis are assigned to metformin or a placebo treatment in a randomized controlled triala study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects. No difference is found between the groups, and so the researchers conclude that metformin has no benefit. 

One problem here is that not having a diabetes diagnosis is not the same as not having diabetes. “More than 37 million people in the United States have diabetes, and 1 in 5 of them don’t know they have it. 96 million US adults—over a third—have prediabetes, and more than 8 in 10 of them don’t know they have it.”1Diabetes Fast Facts. Centers for Disease Control and Prevention. December 17, 2021. Viewed August 4, 2022. The chances are fairly high that some of the people in the study actually have diabetes or at least prediabetes. 

Hidden metabolic and diabetes status shouldn’t be a big issue in a large study where randomization is expected to evenly assign people across the different treatment groups. However, in a small study, having two or three more people with prediabetes in one group compared to another could skew the results.

Even further, anticancer activity of metformin may be seen among people without diabetes but with other metabolic abnormalities compared to people with no metabolic abnormalities. Some intriguing results show that not just diabetes but the metabolic status of people with primary breast cancer—or perhaps even the tumors—can impact outcomes. Three studies we’ve reviewed have found different trends in a markera chemical or substance, such as certain proteins or genetic material, that are associated with the presence of cancer or a change in status or prognosis; these markers can be detected in blood, urine, or tissue. Tumor markers are not direct measures of clinical outcomes such as survival or metastasis, and if a therapy or treatment shows an impact only on tumor markers, we cannot surmise that it will affect survival. of tumor proliferation depending on metabolic markers among people without diabetes

  • Metformin use led to a decrease in proliferation among nondiabetic women with breast cancer and higher insulin resistance, but an increase in proliferation among women with lower resistance.2Bonanni B, Puntoni M et al. Dual effect of metformin on breast cancer proliferation in a randomized presurgical trial. Journal of Clinical Oncology. 2012 Jul 20;30(21):2593-600. 
  • Another study found a similar but nonsignificant (weak) trendan apparent change due to a therapy, close to but not achieving full statistical significance (this is the CancerChoices definition; other researchers and studies may define this differently toward opposite effects on proliferation among nondiabetic people with breast cancer and insulin resistance compared to normal insulin sensitivity.3Cazzaniga M, DeCensi A et al. The effect of metformin on apoptosis in a breast cancer presurgical trial. British Journal of Cancer. 2013 Nov 26;109(11):2792-7. 
  • A third study found lower proliferation only among nondiabetic people with breast cancer and high insulin resistance, and a weak trend toward higher proliferation among people with low insulin resistance.4DeCensi A, Puntoni M et al. Differential effects of metformin on breast cancer proliferation according to markers of insulin resistance and tumor subtype in a randomized presurgical trial. Breast Cancer Research and Treatment. 2014 Nov;148(1):81-90.

Another study found no evidence of effect of metformin overall, but lower risk of progression and mortality among the subset of people with tumors with higher glucose metabolism when metformin was added to chemotherapy.5Lee Y, Joo J et al. Randomized phase II study of platinum-based chemotherapy plus controlled diet with or without metformin in patients with advanced non-small cell lung cancer. Lung Cancer. 2021 Jan;151:8-15.

We suspect that the conflicting and sometimes confusing findings across studies may be due in part to a lack of enough attention to the metabolic/diabetes status among people in the study. Blanket conclusions about effects may be oversimplified to the point of being misleading. To help us as we interpret study findings, we separate studies into those limited to people with diabetes and those including people without diabetes. In some cases, we’ve had to make our best guess, as the study authors do not provide this information.

Other research analysis approaches find fault with many of the studies here, and in fact with many observational studies overall. One such fault is failing to account for immortal time bias, the time during the observation  period in which the outcome event cannot occur, for example if the observation or data collection start before people begin treatment. Bias is introduced when this period of “immortality” is misclassified or excluded during analysis.6Catalogue of Bias. Immortal time bias. Centre for Evidence-Based Medicine. Viewed August 4, 2022. “The association between metformin and pancreatic cancer survival has been greatly exaggerated in previous cohort studies due to the wide existence of immortal time bias.”7Wei M, Liu Y, Bi Y, Zhang Z. Metformin and pancreatic cancer survival: real effect or immortal time bias? International Journal of Cancer. 2019 Mar;145(7):1822-1828.

We do our best to report and interpret the results we find, but better study designs and reporting are definitely needed to come to solid conclusions about the effectiveness of metformin regarding benefits as an adjunctivea therapy connected or added to a main treatment or therapy, not used alone treatment for nondiabetic people with cancer.

Improving treatment outcomes

Is metformin linked to improved survival? Is it linked to less cancer growth or metastasis? Does it enhance the anticancer action of other treatments or therapies? We present the evidence.

People with type 2 diabetes are at higher risk for poor cancer outcomes due to specific diabetes-related processes that promote certain cancer types. Metformin thwarts some of these cancer-promoting processes and helps correct terrainthe internal conditions of your body, including nutritional status, fitness, blood sugar balance, hormone balance, inflammation and more imbalances due to diabetes. As a result, we are not surprised to find that metformin shows the biggest benefits among people with cancer types linked to type 2 diabetes, insulin resistancea condition in which cells in your muscles, fat, and liver don’t respond well to insulin and can’t efficiently take up glucose from your blood for energy, and/or high blood sugar.

Cancer as a whole

Modest evidencesignificant effects in at least three small but well-designed randomized controlled trials (RCTs), or one or more well-designed, mid-sized clinical studies of reasonably good quality (RCTs or observational studies), or several small studies aggregated into a meta-analysis (this is the CancerChoices definition; other researchers and studies may define this differently) of lower cancer-specific mortality among people with diabetes treated with metformin

Advanced cancer

No evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments on survival or tumor response among people with advanced or metastatic cancer (not specific to diabetics) treated with metformin in a combined analysis of studies

No evidence of an effect on overall or progression-free survival among nondiabetic women with metastatic breast cancer treated with metformin in a combined analysis of studies

Bladder cancer

Modest evidence of lower cancer-specific mortality among people with both bladder cancer and diabetes treated with metformin

Modest evidence of better progression-free survivalthe time during and after treatment of a disease that a patient lives without disease progression (worsening) among people with both bladder cancer and diabetes treated with metformin

Brain and nervous system cancers

Modest evidence of better overall survival among people with glioma or glioblastoma and diabetes treated with metformin

Preliminary evidencesignificant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect (this is the CancerChoices definition; other researchers and studies may define this differently) of longer progression-free intervals among people with glioblastoma and diabetes receiving radiation therapy and also treated with metformin

Preliminary evidence of better progression-free survival among people with glioblastoma (not specific to diabetes) treated with metformin compared to no metformin at baseline, but no evidence of an effect with metformin during radiotherapy

Weak evidenceone or more case studies, supported by animal evidence OR small treatment effects of limited clinical significance OR studies with no controls OR weak trends of effects (this is the CancerChoices definition; other researchers and studies may define this differently) of lower cancer-specific mortality among people with glioblastoma treated with metformin compared to no metformin at baseline, but no evidence of an effect with metformin during radiotherapy

Breast cancer

Modest evidence of better survival among people with breast cancer and diabetes treated with metformin

Preliminary evidence of better relapse-free survival after exemestane treatment among women with diabetes and breast tumors with high insulin-like growth factor type 1 receptor (IGF‐1R) expression treated with metformin

Weak evidence of lower risk of distant metastases among people with triple negative breast cancer and diabetes treated with metformin

Preliminary evidence of better response rates among people with breast cancer and diabetes treated with metformin

No evidence of an effect on progression-free or overall survival among nondiabetic women with breast cancer treated with metformin in combined analyses of studies

Modest evidence of a lower markera chemical or substance, such as certain proteins or genetic material, that are associated with the presence of cancer or a change in status or prognosis; these markers can be detected in blood, urine, or tissue. Tumor markers are not direct measures of clinical outcomes such as survival or metastasis, and if a therapy or treatment shows an impact only on tumor markers, we cannot surmise that it will affect survival. of tumor proliferation among nondiabetic women with invasive breast cancer treated with metformin before surgery

No evidence of an effect on overall survival or cancer-specific survival among people with breast cancer (not specific to diabetes) treated with metformin in combined analyses of studies

Preliminary evidence of lower risk of relapse after exemestane treatment among people with postmenopausal hormone receptor positive breast cancer (likely with diabetes) treated with metformin

Preliminary evidence of fewer cases of metastasis after chemotherapy and hormone therapy among nondiabetic women with breast cancer treated with metformin

Modest evidence of lower markers of tumor proliferation among nondiabetic people with breast cancer and higher insulin resistance treated with metformin

Modest evidence of a lower marker of proliferation among nondiabetic people with HER2-positive DCIS lesions, and especially ER-positive/HER2-positive DCIS, treated with metformin

Modest evidence of higher objective response rate among nondiabetic people with breast cancer treated with metformin

Colorectal cancer

Modest evidence of lower mortality, including cancer-specific mortality, among people with colorectal cancer and diabetes treated with metformin

Preliminary evidence of substantially lower risk of metastasis and greater reductions in a tumor markera chemical or substance, such as certain proteins or genetic material, that are associated with the presence of cancer or a change in status or prognosis; these markers can be detected in blood, urine, or tissue. Tumor markers are not direct measures of clinical outcomes such as survival or metastasis, and if a therapy or treatment shows an impact only on tumor markers, we cannot surmise that it will affect survival. among people with colorectal cancer and diabetes treated with metformin

Modest evidence of moderately lower cancer-specific mortality among people with diabetes and colorectal cancer, including metastatic cancer, treated with metformin

Gastrointestinal cancer

Colorectal cancer and pancreatic cancer are listed separately.

Preliminary evidence of tumor suppression among nondiabetic people with gastrointestinal cancer (including colorectal, pancreatic, gastroesophageal, and bile duct cancers) treated with chemotherapy and metformin

No evidence of an effect on tumor proliferation among people with esophageal squamous cell carcinoma (not specific to diabetes) treated with metformin in a small study

Modest evidence of better survival among people with liver cancer and diabetes treated with metformin

Weak evidence of lower mortality among people with stomach cancer and type 2 diabetes treated with metformin

Gynecological cancer

Ovarian cancer is listed separately.

No evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments among women with stage 1–4 cervical cancer treated with metformin compared to people not treated with metformin, whether with diabetes or not

Modest evidencesignificant effects in at least three small but well-designed randomized controlled trials (RCTs), or one or more well-designed, mid-sized clinical studies of reasonably good quality (RCTs or observational studies), or several small studies aggregated into a meta-analysis (this is the CancerChoices definition; other researchers and studies may define this differently) of lower mortality among people with endometrial cancer and diabetes treated with metformin

Modest evidence of lower risk of relapse among reproductive-aged women with atypical endometrial hyperplasia or early endometrial cancer (not specific to diabetes) treated with metformin

Insufficient evidencepreclinical evidence only OR clinical studies with such poor or unclear methodology that no conclusion can be drawn OR conflicting findings across clinical studies with no preponderance of evidence in one direction; conflicting evidence occurs when studies find conflicting effects (positive effect vs no effect or negative effect) with the same treatment and the same general study population (same cancer type, for example) (this is the CancerChoices definition; other researchers and studies may define this differently) of tumor response among people with endometrial cancer (not specific to diabetes) treated with metformin

Head, neck, and oral cancer

Modest evidence of better survival among people with head and neck cancer and diabetes treated with metformin

No evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. on survival or tumor proliferation among people with head and neck cancer (not specific to diabetes) treated with metformin in a several studies

Kidney cancer

Preliminary evidence of lower risk of mortality among people with kidney cancer and diabetes treated with metformin

Modest evidence of lower risk of progression among people with kidney cancer and diabetes treated with metformin

Leukemia

Preliminary evidence of lower risk of relapse among people with acute lymphoblastic leukemia (without diabetes or mixed diabetic and nondiabetic people) treated with metformin in addition to chemotherapy

Lung cancer

Modest evidence of lower mortality among people with type 2 diabetes and lung cancer treated with metformin

No evidence of an effect on risk of metastasis among people with lung cancer and diabetes treated with metformin in a preliminary study

No evidence of an effect on overall survival or progression-free survival among people with lung cancer (not specific to diabetes) treated with metformin in combined analyses of studies

Preliminary evidence of lower risk of progression and mortality among people with tumors with higher glucose metabolism treated with metformin

Lymphoma

Weak evidence of better survival among people with diffuse large B-cell lymphoma with diabetes treated with metformin

No evidence of an effect on response rate or survival among people with diffuse large B-cell lymphoma treated with metformin in a preliminary study

Melanoma

No evidence of objective response among nondiabetic people with melanoma treated with metformin in small studies

Modest evidence of higher melanoma-specific survival among people with melanoma (not specific to diabetes) treated with metformin

No evidence of objective response among people with melanoma (not specific to diabetes) treated with metformin in small studies

Ovarian cancer

Modest evidence of lower mortality and higher progression-free survival among people with ovarian cancer and diabetes treated with metformin

Insufficient (conflicting) evidencepreclinical evidence only OR clinical studies with such poor or unclear methodology that no conclusion can be drawn OR conflicting findings across clinical studies with no preponderance of evidence in one direction; conflicting evidence occurs when studies find conflicting effects (positive effect vs no effect or negative effect) with the same treatment and the same general study population (same cancer type, for example) (this is the CancerChoices definition; other researchers and studies may define this differently) of an effect on survival or progression among people with ovarian cancer (not specific to diabetes) treated with metformin

Pancreatic cancer

Modest evidence of lower mortality among people with pancreatic cancer and diabetes treated with metformin

Modest evidence of lower mortality among people with pancreatic cancer (not specific to diabetes) treated with metformin

Prostate cancer

Modest evidence of lower mortality among people with prostate cancer and diabetes treated with metformin

Insufficient evidence of an effect on mortality, metastases, or disease progression among people with prostate cancer (not specific to diabetes) treated with metformin

Metformin combined with other therapies

Weak evidence of lower PSA levels in a man with recurrent castration-resistant prostate cancer and increasing PSA levels treated with conventional care and metformin

Weak evidence of disease control among people with metastatic colorectal cancer previously treated with oral metformin plus chemotherapy

Optimizing your body terrain

Does metformin promote an environment within your body that is less supportive of cancer development, growth, or spread? We present the evidence.

See Optimizing Your Body Terrain ›

Find medical professionals who specialize in managing body terrain factors: Finding Integrative Oncologists and Other Practitioners ›

Body weight

Good evidencesignificant effects in one large or several mid-sized and well-designed clinical studies (randomized controlled trials (RCTs) with an appropriate placebo or other strong comparison control or observational studies that control for confounds) (this is the CancerChoices definition; other researchers and studies may define this differently) of lower body weight among nondiabetic people with cancer treated with metformin

Good evidence of lower body weight among people with cancer (not specific to diabetes) treated with metformin for longer than 1 to 5 weeks

Preliminary evidencesignificant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect (this is the CancerChoices definition; other researchers and studies may define this differently) of lower body weight among nondiabetic people with endometrial hyperplasia without atypia treated with metformin

Modest evidencesignificant effects in at least three small but well-designed randomized controlled trials (RCTs), or one or more well-designed, mid-sized clinical studies of reasonably good quality (RCTs or observational studies), or several small studies aggregated into a meta-analysis (this is the CancerChoices definition; other researchers and studies may define this differently) of lower body weight and waist circumference among people with metabolic imbalances other than diabetes treated with metformin

High blood sugar and insulin resistance

The FDA has approved metformin for reducing high blood sugar in people with type 2 diabetes, with substantial evidence of benefit for this condition. Use in people who don’t have type 2 diabetes is considered off-label use. Here we summarize only the evidence for metformin’s effects on blood glucose and insulin among people without type 2 diabetes or mixed groups of diabetic and nondiabetic people.

Preliminary evidence of lower blood glucose after a meal but not while fasting among people with blood cancers without diabetes or prediabetes at baseline treated with metformin

Good evidence of lower levels of blood sugar among nondiabetic people with breast or endometrial cancer treated with metformin

Insufficient (conflicting) evidencepreclinical evidence only OR clinical studies with such poor or unclear methodology that no conclusion can be drawn OR conflicting findings across clinical studies with no preponderance of evidence in one direction; conflicting evidence occurs when studies find conflicting effects (positive effect vs no effect or negative effect) with the same treatment and the same general study population (same cancer type, for example) (this is the CancerChoices definition; other researchers and studies may define this differently) of an effect on insulin resistance among nondiabetic people with breast, endometrial, or ovarian cancer treated with metformin

Preliminary evidence of lower insulin levels among nondiabetic people with colorectal cancer treated with metformin

No evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. on a marker of glycemic control among men with normal glycemia and locally advanced prostate cancer treated with metformin in a small study

Preliminary evidence of lower levels of insulin or insulin resistance among people without cancer or diabetes treated with metformin

Preliminary evidence of lower levels of insulin, insulin resistance, and/or blood sugar among overweight or obese people or with impaired glucose tolerance or insulin resistance treated with metformin

Hormone imbalance

Changes in hormone levels seen in the studies here may not be beneficial in every situation. Your oncology team needs to determine whether any changes would be favorable for your condition.

Good evidence of lower levels of many sex hormones among mostly nondiabetic people with cancer treated with metformin

Modest evidence of lower markers of insulin-like growth factors among people with cancer treated with metformin

Preliminary evidence of lower IGF-1 levels among nondiabetic people with major depressive disorder treated with metformin

Preliminary evidence of lower levels of insulin-like growth factors among nondiabetic or mixed groups of people with breast or endometrial cancer treated with metformin

Modest evidence of higher levels of adiponectin—protective against insulin resistance/diabetes and atherosclerosis—among women with polycystic ovary syndrome (not specific to cancer) treated with metformin

Modest evidence of lower levels of leptin—a hormone that suppresses appetite—among people with cancer treated with metformin

Preliminary evidence of lower levels of thyroid stimulating hormone among people with thyroid nodules and insulin resistance treated with metformin

Immune function

Increased immune system activation is not always beneficial, so your oncology team needs to determine whether immune activation would be favorable in your situation.

Weak evidenceone or more case studies, supported by animal evidence OR small treatment effects of limited clinical significance OR studies with no controls OR weak trends of effects (this is the CancerChoices definition; other researchers and studies may define this differently) of higher immune activation among people with cancer (not specific to diabetes) treated with metformin

Inflammation

Good evidence of lower or more balanced markers of inflammation among people with cancer (not specific to diabetes) treated with metformin

Modest evidence of lower markers of inflammation among people with polycystic ovary syndrome (not specific to diabetes) treated with metformin

Preliminary evidence of lower markers of inflammation among nondiabetic people with major depressive disorder treated with metformin

Oxidative stress

Preliminary evidence of lower markers of oxidative stressan imbalance between free radicals and antioxidants in your body in which antioxidant levels are lower than normal; this imbalance can cause harmful oxidation reactions in your body chemistry during FOLFOX-4 regimen among people with colorectal cancer (not specific to diabetes) treated with metformin

Preliminary evidence of a lower marker of oxidation among nondiabetic people with major depressive disorder treated with metformin

Your microbiome

Preliminary evidence of changes in the composition of the microbiomethe collection of microbes living on and within your body, including beneficial increases in butyrate among among overweight or obese adults without medication-treated diabetes with solid tumor cancers treated with metformin

Metformin combined with other therapies or practices

Weak evidence of lower body weight, waist circumference, blood sugar, and insulin resistance, as well as changes in thyroid hormone levels among people newly diagnosed with insulin resistance or diabetes participating in a diet and exercise intervention and treated with metformin

Preliminary evidence of weight loss and lower insulin and leptina hormone that helps regulate energy balance by inhibiting hunger levels among nondiabetic people participating in physical activity and treated with metformin

Managing side effects and promoting wellness

Is metformin linked to fewer or less severe side effects or symptoms? Is it linked to less toxicity from cancer treatment? Does it support your quality of life or promote general well-being? We present the evidence.

Blood-related symptoms

Preliminary evidencesignificant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect (this is the CancerChoices definition; other researchers and studies may define this differently) of lower incidence of grade 3/4 neutropeniaan abnormally low number of neutrophils in the blood, leading to increased susceptibility to infection among nondiabetic women with metastatic breast cancer treated with metformin

Body composition and cachexia

Preliminary evidence of short-term lower gains in body weight but no evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. on waist circumference among men with normal glycemia and locally advanced prostate cancer treated with metformin

Cognitive difficulties

No evidence of an effect on cognitive domain scores among overweight or obese postmenopausal women with breast cancer treated with metformin in a preliminary study

Preliminary evidence of better performance on tests of working memory and auditory-verbal memory, and a weak trendan apparent change due to a therapy, close to but not achieving full statistical significance (this is the CancerChoices definition; other researchers and studies may define this differently toward better reaction time, among survivors of pediatric brain tumors without unstable or insulin-dependent diabetes  treated with metformin

Neuropathy and other neurological symptoms

Preliminary evidence of lower rate of grade 2 and 3 neuropathy, lower neurotoxicity scores, and other indicators of neuropathy during chemotherapy among people with colorectal cancer (not specific to diabetes) treated with metformin

Pain

Preliminary evidence of lower scores of pain related to neuropathy during chemotherapy among people with colorectal cancer (not specific to diabetes) treated with metformin

Other side effects

Preliminary evidence of lower endometrial thickness—a side effect of tamoxifen treatment—during tamoxifen treatment among postmenopausal women with hormone receptor-positive breast cancer (not specific to diabetes) treated with metformin

Side effects not specific to cancer

Good evidencesignificant effects in one large or several mid-sized and well-designed clinical studies (randomized controlled trials (RCTs) with an appropriate placebo or other strong comparison control or observational studies that control for confounds) (this is the CancerChoices definition; other researchers and studies may define this differently) of lower risk of fractures among people with diabetes (not specific to cancer) treated with metformin

Preliminary evidence of lower depression scores among nondiabetic people with major depressive disorder treated with metformin

Metformin combined with other therapies or practices

Metformin and lifestyle practices: preliminary evidence of better abdominal girth, body mass index, weight, and systolic blood pressure, but no evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. on insulin resistancea condition in which cells in your muscles, fat, and liver don’t respond well to insulin and can’t efficiently take up glucose from your blood for energy, during androgen deprivation therapy among men with prostate cancer treated with metformin, following a low-glycaemic index diet, and participating in an exercise program

Reducing cancer risk

Is metformin linked to lower risks of developing cancer or of recurrence? We present the evidence.

People with type 2 diabetes are at higher risk for cancer due to specific diabetes-related processes that promote cancer. Metformin thwarts some of these cancer-promoting processes and helps correct terrain imbalances due to diabetes. As a result, we are not surprised to find that metformin shows the biggest benefits among people with cancer types linked to type 2 diabetes, insulin resistancea condition in which cells in your muscles, fat, and liver don’t respond well to insulin and can’t efficiently take up glucose from your blood for energy, and/or high blood sugar.

In the great majority of observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies (which is most of the available studies) of metformin’s effect on cancer risk, metformin use is limited almost entirely to people using it for diabetes. Most of metformin’s benefits related to cancer risk are found among people with diabetes, insulin resistance, and/or high blood sugar.

Cancer as a whole

Modest evidencesignificant effects in at least three small but well-designed randomized controlled trials (RCTs), or one or more well-designed, mid-sized clinical studies of reasonably good quality (RCTs or observational studies), or several small studies aggregated into a meta-analysis (this is the CancerChoices definition; other researchers and studies may define this differently) of lower risk of cancer as a whole among people with diabetes treated with metformin

No evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. on cancer-specific mortality among people at high risk of type 2 diabetes treated with metformin in a very large study

Bladder or urothelial cancer

Modest evidence of lower risk of recurrence among people with both bladder cancer and diabetes treated with metformin

Modest evidence of lower risk of recurrence among people with urothelial cancer and diabetes treated with metformin

Breast cancer

No evidence of an effect on recurrence among people with breast cancer and diabetes treated with metformin in a combined analysis of studies

Preliminary evidencesignificant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect (this is the CancerChoices definition; other researchers and studies may define this differently) of lower risk of recurrence among diabetic people with hormone-receptor positive but not negative breast cancer treated with metformin

Insufficient evidencepreclinical evidence only OR clinical studies with such poor or unclear methodology that no conclusion can be drawn OR conflicting findings across clinical studies with no preponderance of evidence in one direction; conflicting evidence occurs when studies find conflicting effects (positive effect vs no effect or negative effect) with the same treatment and the same general study population (same cancer type, for example) (this is the CancerChoices definition; other researchers and studies may define this differently) of an effect on risk of breast cancer among people with type 2 diabetes treated with metformin, with possibly lower risk with use for 3 years or longer

Modest evidence of lower breast cancer-specific mortality among people without cancer at baseline with diabetes treated with metformin

Insufficient evidence of lower risk of recurrence among people with breast cancer (not specific to diabetes) using metformin

Modest evidence of slightly lower risk of breast cancer and lower breast cancer-specific mortality among people without cancer at baseline (not specific to diabetes) treated with metformin

Preliminary evidence of fewer grade 3 tumors or triple negative tumors, but higher incidence of ER or PR positive tumors, among people with breast cancer (not specific to diabetes) using metformin at the time of diagnosis

Preliminary evidence of lower Breast Imaging Reporting and Data System (BIRADS) scores and positive pathological biopsy rate among overweight/obese premenopausal women without diabetes treated with metformin

Colorectal cancer

Weak evidence of lower risk of recurrence among people with colorectal cancer and diabetes treated with metformin, with stronger effects among people with early stage cancer

Modest evidence of lower risk of colorectal cancer among people with diabetes treated with metformin

Weak evidence of fewer rectal aberrant crypt foci among people with impaired glucose tolerance treated with higher doses of metformin

No evidence of an effect on the percentage change in the number or size of colorectal and duodenal polyps among nondiabetic people with familial adenomatous polyposis treated with metformin in a preliminary study

Gastrointestinal cancer

Colorectal cancer and pancreatic cancer are listed separately.

Preliminary (conflicting) evidencesignificant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect (this is the CancerChoices definition; other researchers and studies may define this differently) of slightly lower risk of esophageal cancer among people with type 2 diabetes treated with metformin

No evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. on markersa chemical or substance, such as certain proteins or genetic material, that are associated with the presence of cancer or a change in status or prognosis; these markers can be detected in blood, urine, or tissue. Tumor markers are not direct measures of clinical outcomes such as survival or metastasis, and if a therapy or treatment shows an impact only on tumor markers, we cannot surmise that it will affect survival. of cell proliferation or cell death among nondiabetic people with Barrett’s esophagus treated with metformin in a preliminary study

Preliminary (conflicting) evidence of lower risk of recurrence among people with liver cancer (hepatocellular carcinoma) and diabetes treated with metformin

Good evidencesignificant effects in one large or several mid-sized and well-designed clinical studies (randomized controlled trials (RCTs) with an appropriate placebo or other strong comparison control or observational studies that control for confounds) (this is the CancerChoices definition; other researchers and studies may define this differently) of lower risk of liver cancer among people with diabetes treated with metformin

Modest evidencesignificant effects in at least three small but well-designed randomized controlled trials (RCTs), or one or more well-designed, mid-sized clinical studies of reasonably good quality (RCTs or observational studies), or several small studies aggregated into a meta-analysis (this is the CancerChoices definition; other researchers and studies may define this differently) of lower risk of stomach cancer among people with type 2 diabetes treated with metformin, although with a risk of bias in studies that may contribute to overestimating the benefit

Gynecological cancer

Ovarian cancer is listed separately.

Modest evidence of lower risk of gynecological cancers as a whole among people with diabetes treated with metformin

Modest evidence of lower risk of cervical cancer among people with diabetes treated with metformin

Modest evidence of lower risk of recurrence among diabetic people with endometrial cancer treated with metformin

Insufficient evidencepreclinical evidence only OR clinical studies with such poor or unclear methodology that no conclusion can be drawn OR conflicting findings across clinical studies with no preponderance of evidence in one direction; conflicting evidence occurs when studies find conflicting effects (positive effect vs no effect or negative effect) with the same treatment and the same general study population (same cancer type, for example) (this is the CancerChoices definition; other researchers and studies may define this differently) of an effect on risk of endometrial cancer among people with diabetes treated with metformin

Insufficient evidence of an effect on endometrial cancer or on regression of endometrial hyperplasia (not specific to diabetes) treated with metformin

Head and neck cancer

Modest evidence of lower risk of head and neck cancer among people with diabetes treated with metformin

No evidence of an effect on recurrence among people with head and neck cancer without diabetes or mixed groups  of diabetic and nondiabetic people treated with metformin in a combined analysis of studies

Weak evidenceone or more case studies, supported by animal evidence OR small treatment effects of limited clinical significance OR studies with no controls OR weak trends of effects (this is the CancerChoices definition; other researchers and studies may define this differently) of clinical response among nondiabetic people with oral premalignant lesions treated with metformin

Kidney cancer

No evidence of an effect on risk of recurrence among people with kidney cancer (not specific to diabetes) treated with metformin in mid-sized studies

Leukemia

No evidence of an effect on risk of recurrence among people with acute lymphoblastic leukemia (not specific to diabetes) treated with metformin in a preliminary study

Lung cancer

No evidence of an effect on risk of recurrence among people with lung cancer and diabetes treated with metformin in a preliminary study

Modest evidence of a slightly lower risk of lung cancer among people with diabetes treated with metformin

No evidence of an effect on risk of lung cancer among people (not specific to diabetes) treated with metformin

Ovarian cancer

Weak evidence of substantially longer recurrence-free survival among diabetic people with ovarian cancer treated with metformin

No evidence of an effect on risk of recurrence after treatment with paclitaxel plus carboplatin among people with epithelial ovarian cancer without diabetes treated with metformin

Weak evidence of lower risk of recurrence among people with ovarian cancer (not specific to diabetes) treated with metformin

Modest evidence of lower risk of ovarian cancer among women with diabetes treated with metformin

Pancreatic cancer

Weak evidence of lower risk of recurrence among people with pancreatic cancer (mostly with diabetes) treated with metformin

Modest evidence of lower risk of pancreatic cancer among people with diabetes treated with metformin

Prostate cancer

Modest evidence of lower risk of recurrence among people with prostate cancer and diabetes treated with metformin

Preliminary evidence of lower risk of recurrence among people with prostate cancer (not specific to diabetes) treated with metformin

Insufficient evidence of an effect on risk of prostate cancer among people with diabetes treated with metformin

Insufficient evidence of an effect on risk of prostate cancer among people (not specific to diabetes) treated with metformin

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

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

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Keep reading about metformin

Authors

Nancy Hepp, MS

Lead Researcher
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Ms. Hepp is a researcher and communicator who has been writing and editing educational content on varied health topics for more than 20 years. She serves as lead researcher and writer for CancerChoices and also served as the first program manager. Her graduate work in research and cognitive psychology, her master’s degree in instructional design, and her certificate in web design have all guided her in writing and presenting information for a wide variety of audiences and uses. Nancy’s service as faculty development coordinator in the Department of Family Medicine at Wright State University also provided experience in medical research, plus insights into medical education and medical care from the professional’s perspective.

Nancy Hepp, MS Lead Researcher

Andrew Jackson, ND

Research Associate
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Andrew Jackson, ND, serves as a CancerChoices research associate. As a naturopathic physician practicing in Kirkland, Washington, he teaches critical evaluation of the medical literture at Bastyr University in Kenmore, Washington. His great appreciation of scientific inquiry and the scientific process has led him to view research with a critical eye.

Andrew Jackson, ND Research Associate

Reviewers

Laura Pole, MSN, RN, OCNS

Senior Clinical Consultant
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Laura Pole is senior clinical consultant for CancerChoices. Laura is an oncology clinical nurse specialist who has been providing integrative oncology clinical care, navigation, consultation, and education services for over 40 years. She is the co-creator and co-coordinator of the Integrative Oncology Navigation Training at Smith Center for Healing and the Arts in Washington, DC. Laura also manages the “Media Watch Cancer News That You Can Use” listserv for Smith Center/Commonweal. In her role as a palliative care educator and consultant, Laura has served as statewide Respecting Choices Faculty for the Virginia POST (Physician Orders for Scope of Treatment) Collaborative as well as provided statewide professional education on palliative and end-of-life care for the Virginia Association for Hospices and Palliative Care.

For CancerChoices, Laura curates content and research, networks with clinical and organizational partners, brings awareness and education of integrative oncology at professional and patient conferences and programs, and translates research into information relevant to the patient experience as well as clinical practice.

Laura sees her work with CancerChoices as a perfect alignment of all her passions, knowledge and skills in integrative oncology care. She is honored to serve you.

Laura Pole, MSN, RN, OCNS Senior Clinical Consultant

Dr. Fuller-Shavel is a GMC-registered integrative medicine doctor with degrees in medicine and natural sciences from the University of Cambridge. Dr. Fuller-Shavel is a fellow of the College of Medicine and the vice chair for BSIO (British Society for Integrative Oncology). Alongside her science and medical training, Dr. Fuller-Shavel holds multiple qualifications in nutrition, integrative medicine, health coaching, herbal medicine, yoga, mindfulness and other mind-body approaches.

Dr. Fuller-Shavel is the director of Synthesis Clinic, an award-winning multidisciplinary integrative medicine practice in Hampshire, UK, specializing in women’s health, gut health (microbiome and gut-brain axis) and mental health. She combines her clinical work in women’s health and supporting patients with breast and gynecological cancer with education and training for healthcare professionals and research in precision cancer medicine and precision nutrition.

Nina Fuller-Shavel, MB, BChir, MA Hons, FBANT, IFMCP, DipIM, PG Cert RYT300

Last update: April 19, 2024

Last full literature review: March 2022

CancerChoices provides information about integrativein cancer care, a patient-centered approach combining the best of conventional care, self care, and evidence-informed complementary care in an integrated plan cancer care. We review complementaryin cancer care, complementary care involves the use of therapies intended to enhance or add to standard conventional treatments; examples include supplements, mind-body approaches such as yoga or psychosocialtherapy, and acupuncture therapies and self carelifestyle actions and behaviors that may impact cancer outcomes; examples include eating health-promoting foods, limiting alcohol, increasing physical activity, and managing stress practices to help patients and professionals explore and integrate the best combination of conventionalthe cancer care offered by conventionally trained physicians and most hospitals; examples are chemotherapy, surgery, and radiotherapy and complementary therapies and practices for each person.

Our staff have no financial conflicts of interest to declare. We receive no funds from any manufacturers or retailers gaining financial profit by promoting or discouraging therapies mentioned on this site.

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