Cited by 457Metabolism, Diabetes, and CancerCancer Risks and FactorsNutritional Studies and Diet

Metformin and Cancer Risk and Mortality: A Systematic Review and Meta-analysis Taking into Account Biases and Confounders

Open access
Gandini, Sara, Puntoni, Matteo, Heckman-Stoddard, Brandy M., Dunn, Barbara K., Ford, Leslie, DeCensi, Andrea, Szabo, Eva·2014·Cancer Prevention Research

Published version of a preprint

Abstract

Previous meta-analyses have shown that the antidiabetic agent metformin is associated with reduced cancer incidence and mortality. However, this effect has not been consistently demonstrated in animal models and recent epidemiologic studies. We performed a meta-analysis with a focus on confounders and biases, including body mass index (BMI), study type, and time-related biases. We identified 71 articles published between January 1, 1966, and May 31, 2013, through Pubmed, ISI Web of Science (Science Citation Index Expanded), Embase, and the Cochrane library that were related to metformin and cancer incidence or mortality. Study characteristics and outcomes were abstracted for each study that met inclusion criteria. We included estimates from 47 independent studies and 65,540 cancer cases in patients with diabetes. Overall cancer incidence was reduced by 31% [summary relative risk (SRR), 0.69; 95% confidence interval (CI), 0.52–0.90], although between-study heterogeneity was considerable (I2 = 88%). Cancer mortality was reduced by 34% (SRR, 0.66; 95% CI, 0.54–0.81; I2 = 21%). BMI-adjusted studies and studies without time-related biases also showed significant reduction in cancer incidence (SRR, 0.82; 95% CI, 0.70–0.96 with I2 = 76% and SRR, 0.90; 95% CI, 0.89–0.91 with I2 = 56%, respectively), albeit with lesser magnitude (18% and 10% reduction, respectively). However, studies of cancer mortality and individual organ sites did not consistently show significant reductions across all types of analyses. Although these associations may not be causal, our results show that metformin may reduce cancer incidence and mortality in patients with diabetes However, the reduction seems to be of modest magnitude and not affecting all populations equally. Clinical trials are needed to determine if these observations apply to nondiabetic populations and to specific organ sites. Cancer Prev Res; 7(9); 867–85. ©2014 AACR.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1158/1940-6207.capr-13-0424

Cites

113 of 113 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Long-term use of metformin in type 2 diabetes patients is linked to a decline in tumor incidence and a reduced rate of cancer-related deaths.

    “long-term use of metformin in type 2 diabetes patients has been linked to a decline in tumor incidence and a reduced rate of cancer-related deaths.192–196”

    From Drug repurposing for cancer therapy (2024) · cites this paper as [192]

    The Abstract and Results (page unavailable) report lower overall cancer incidence and cancer mortality among diabetic metformin users, supporting the claimed association. The analysis does not establish that the association applies specifically to long-term use; the Discussion also says the mortality reduction lost statistical significance when time-biased studies were excluded. (LLM, conf=0.86)

    Experimental — accuracy not yet measured
  • Retrospective clinical studies have found that metformin use is associated with improved cancer outcomes, reductions in cancer incidence, and decreased cancer mortality.

    “Furthermore, retrospective clinical studies have found that metformin use is associated with improved cancer outcomes, reductions in cancer incidence, and decreased cancer mortality (Evans et al., 2005; Franciosi et al., 2013; Gandini et al., 2014; Lee et al., 2012; Noto et al., 2012).”

    From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Gandini et al., 2014

  • Extensive support for a protective effect of metformin against cancer has been provided by numerous, but not all studies.

    “Extensive support for a protective effect of metformin against cancer has been provided by numerous, but not all studies (237, 238).”
  • In a meta-analysis, metformin-treated diabetic patients had a 31% reduction in the incidence of cancer and a 34% reduction in cancer mortality after adjusting for body mass index.

    “In a meta-analysis(255), metformin-treated diabetic patients had a 31% reduction in the incidence of cancer and a 34% reduction in cancer mortality after adjusting for body mass index(255).”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

1 retracted

Flagged first, then by citations

2 of the 115 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Authors
Gandini, S., Puntoni, M., Heckman-Stoddard, B. M., Dunn, B. K., Ford, L., DeCensi, A., & Szabo, E.
Affiliations
  • European Institute of Oncology (IT)
  • Ente Ospedaliero Ospedali Galliera (IT)
  • 3Breast and Gynecologic Cancer Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland.
  • National Institutes of Health (US)
  • National Cancer Institute (US)
Corresponding author
Szabo, Eva
Venue
Cancer Prevention Research
Published
2014-09-01
Volume
7
Issue
9
Pages
867-885
ISSN
  • 1940-6207 (ISSN-L)
  • 1940-6215
OpenAlex
W1976655891
Cited by
457
References
115
Citations by year
2026: 18 · 2025: 29 · 2024: 34 · 2023: 37 · 2022: 47 · 2021: 43 · 2020: 40 · 2019: 43 · 2018: 43 · 2017: 41 · 2016: 43 · 2015: 28 · 2014: 10
FWCI
3.83
Type
journal article
Language
en
Open access
Locations
  • Cancer Prevention Research (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health (Z99 CA999999)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Health Sciences › Medicine › Oncology › Cancer Risks and Factors
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
Keywords
metformin, cancer incidence, cancer mortality, diabetes mellitus, body mass index, confounding, antidiabetic drugs, chemoprevention
MeSH terms
Diabetes Mellitus, Type 2, Humans, Hypoglycemic Agents, Metformin, Neoplasms, Risk

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review