Metformin: Safety and precautions - CancerChoices



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.

Safety and precautions

Interactions with other therapies and effects on cancer outcomes

Some evidence shows toxicity during chemotherapy, higher mortality among people with liver cancer, and worse cancer outcomes among people with lung cancer. No matter which cancer type or chemotherapy you are using, your oncologist and pharmacist need to know if you are taking metformin. Always rely on your medical professional to confirm there are no concerning interactions before taking metformin alongside other treatments. Use metformin only as directed by your licensed physician.

CT/PET scans

Metformin should be stopped at the time of any scan that uses contrast medium, such as CT or PET-CT scans, and for 48 hours afterwards.1Referring Physician / Patient Information Computed Tomography Section Protocol for Management of Patients taking Metformin scheduled for CT Studies with IV Radiographic Contrast Media. UCLA Health. Viewed July 12, 2024.

Effects on cancer outcomes

Cancer as a whole

No evidence of an increase in dose-limiting toxicities during chemotherapy among people with solid tumors treated with metformin in a preliminary trial

Breast cancer

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 higher markers of cancer proliferation among nondiabetic women with breast cancer and with HOMA less than 2.8 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 exemestane pharmacokinetics among people with breast cancer treated with metformin in a preliminary trial

Gastrointestinal cancer

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 higher mortality among people with liver cancer without diabetes treated with metformin

Leukemia

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 dose-limiting toxicity among people with acute lymphoblastic leukemia during treatment with vincristine, dexamethasone, PEG-asparaginase, and doxorubicin (VXLD)

Lung 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 a higher risk of advanced disease and worse survival among people with lung cancer with 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 higher rates of adverse events during platinum-based chemotherapy, concurrent with chest radiotherapy, among nondiabetic people with locally advanced non-small cell lung cancer treated with metformin

Side effects or adverse events

Common side effects

These side effects are common in the first few days of taking metformin.11Side effects of metformin. National Health Service. 24 March 2022. Viewed August 11, 2022; Mark M, Klingbiel D et al. Impact of addition of metformin to abiraterone in metastatic castration-resistant prostate cancer patients with disease progressing while receiving abiraterone treatment (MetAb-Pro): phase 2 pilot study. Clinical Genitourinary Cancer. 2019 Apr;17(2):e323-e328.

Nausea and vomiting
Stomach upset
Diarrhea

Weakness
Metallic taste in the mouth

Tell your doctor or pharmacist promptly if any of these effects persist or worsen after a few days. Stomach symptoms occurring after the first days of treatment may be signs of lactic acidosis, described in “serious side effects” below.

Other mild to moderate side effects and their related recommendations:

Serious side effects

A buildup of lactic acid in the bloodstream (lactic acidosis) is a serious condition: seek treatment immediately. People with poor renal function are at greater risk, and using high doses of metformin may also increase risk.19Higurashi T, Nakajima A. Metformin and colorectal cancer. Frontiers in Endocrinology (Lausanne). 2018 Oct 23;9:622. Symptoms:

  • Unusual fatigue 
  • Dizziness
  • Severe drowsiness
  • Chills
  • Blue/cold skin
  • Muscle pain
  • Rapid and/or difficult breathing
  • Slow and/or irregular heartbeat
  • Abdominal pain with nausea, vomiting or diarrhea 

Other serious side effects of metformin use:

  • Low blood sugar (hypoglycemia) (very rare)
  • Serious allergic reaction (rare)
  • Poor cognitive function20(La Vecchia C, Bosetti C. Metformin: are potential benefits on cancer risk extended to cancer survival? The Oncologist. 2013 Dec;18(12):1245-1247.

Effects on pregnancy or offspring

Similar rates of pregnancy but 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 lower rate of live birth among reproductive-aged women with atypical endometrial hyperplasia or early endometrial cancer (not specific to diabetes) treated with progestin and metformin compared to progestin alone in meta-analysesa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 1 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 and 1 RCTrandomized controlled trial, a 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 of moderate quality21Chae-Kim J, Garg G et al. Outcomes of women treated with progestin and metformin for atypical endometrial hyperplasia and early endometrial cancer: a systematic review and meta-analysis. International Journal of Gynecological Cancer. 2021 Dec;31(12):1499-1505.

Higher body weight among children exposed to metformin before birth compared to no metformin or to insulin in a meta-analysis of 11 RCTs22Xu Q, Xie Q. Long-term effects of prenatal exposure to metformin on the health of children based on follow-up studies of randomized controlled trials: a systematic review and meta-analysis. Archives of Gynecology and Obstetrics. 2019 May;299(5):1295-1303. 

Higher risk of birth defects, especially genital defects among male children, among children whose fathers were treated with metformin during the development of fertilizing sperm compared to no metformin in a very large observational study23Wensink MJ, Lu Y et al. Preconception antidiabetic drugs in men and birth defects in offspring: a nationwide cohort study. Annals of Internal Medicine. 2022 Mar 29.

Do not use (contraindications)

Metformin is not recommended in people with abnormal kidney24Orloff J, Min JY, Mushlin A, Flory J. Safety and effectiveness of metformin in patients with reduced renal function: A systematic review. Diabetes, Obesity & Metabolism. 2021 Sep;23(9):2035-2047. or liver function.25Side effects of metformin. National Health Service. 24 March 2022. Viewed August 11, 2022.

Drug interactions

Many potential drug interactions are associated with metformin. Consult your pharmacist for interactions, and discuss any cautions with your doctor.

Personal story

CancerChoices Senior Clinical Consultant Laura Pole, RN, MSN, OCNS: My colleague, a medical advocate, and I navigated a 50-year-old woman with breast cancer and type 2 diabetes. She takes metformin for her diabetes. She had completed chemotherapy and radiation therapy over a year before working with us, yet still experienced marked fatigue affecting her work and personal life. My colleague ordered a test of her vitamin B12 level, and it came back low. He prescribed B12 injections for her, and within a week her energy came back to pre-chemo levels. For over a year and half her fatigue was blamed on the chemo, when its persistence was likely due to metformin’s effect on her B12 levels.

Helpful links

Keep reading about metformin

Authors

Nancy Hepp, MS

Lead Researcher
View profile

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
View profile

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
View profile

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: July 12, 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.

Learn more

References[+]