Evidence map›Metformin × adverse events & safety›PMID 38291943›Full record

SynthesisJournal of the National Cancer Institute2024

Association of metformin use and cancer incidence: a systematic review and meta-analysis.

Lauren O'Connor, Maeve Bailey-Whyte, Manami Bhattacharya, Gisela Butera, Kaitlyn N Lewis Hardell, Andrew B Seidenberg, Philip E Castle, Holli A Loomans-Kropp

Abstract readMeta-AnalysisSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Journal of the National Cancer Institute, 2024. The graph read 5 numbers from its abstract, feeding 1 cell of the map, but none could be read as for or against, so it casts no vote. It also reports 5 associations that do not count as treatment evidence, such as RR 0.65 (0.37 to 0.93) for overall cancer. Cited by 45 papers, 4 of them syntheses that pooled it.

5numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 4 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

Read, but not usablea number the graph found but could not read as for or against

Overall cancermetformin use vs no metformin use, in prospective cohort studiesan association or prognostic statement, not a treatment comparison · t2dfeeds one cell of the map
RR 0.650.37 to 0.93
Reduced risk for overall cancer was observed in case-control studies (RR = 0.55, 95% confidence interval [CI] = 0.30 to 0.80) and prospective cohort studies (RR = 0.65, 95% CI = 0.37 to 0.93).
FeedsMetformin×adverse events & safety
Hematologic cancer riskmetformin use vs no metformin usean association or prognostic statement, not a treatment comparison · t2dfeeds one cell of the map
RR 0.870.75 to 0.99
Metformin use was associated with reduced gastrointestinal (RR = 0.79, 95% CI = 0.73 to 0.85), urologic (RR = 0.88, 95% CI = 0.78 to 0.99), and hematologic (RR = 0.87, 95% CI = 0.75 to 0.99) cancer risk.
FeedsMetformin×adverse events & safety
Urologic cancer riskmetformin use vs no metformin usean association or prognostic statement, not a treatment comparison · t2dfeeds one cell of the map
RR 0.880.78 to 0.99
Metformin use was associated with reduced gastrointestinal (RR = 0.79, 95% CI = 0.73 to 0.85), urologic (RR = 0.88, 95% CI = 0.78 to 0.99), and hematologic (RR = 0.87, 95% CI = 0.75 to 0.99) cancer risk.
FeedsMetformin×adverse events & safety
Gastrointestinal cancer riskmetformin use vs no metformin usean association or prognostic statement, not a treatment comparison · t2dfeeds one cell of the map
RR 0.790.73 to 0.85
Metformin use was associated with reduced gastrointestinal (RR = 0.79, 95% CI = 0.73 to 0.85), urologic (RR = 0.88, 95% CI = 0.78 to 0.99), and hematologic (RR = 0.87, 95% CI = 0.75 to 0.99) cancer risk.
FeedsMetformin×adverse events & safety
Overall cancermetformin use vs no metformin use, in case-control studiesan association or prognostic statement, not a treatment comparison · t2dfeeds one cell of the map
RR 0.550.30 to 0.80
Reduced risk for overall cancer was observed in case-control studies (RR = 0.55, 95% confidence interval [CI] = 0.30 to 0.80) and prospective cohort studies (RR = 0.65, 95% CI = 0.37 to 0.93).
FeedsMetformin×adverse events & safety

clause the extractor read what became the number

2 · Its place on the map

Where it lands on the map

Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.

supports the treatmentfavours the comparatorno clear differenceread, but no usable result
3 · What it changes

What it adds to each cell

For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.

Metformin×adverse events & safety

No readable resultOpen on the map →What to test next →

21 readable studies in this cell: 8 favour the treatment, 8 find no difference, 5 favour the comparator.

Belief with this paper
0.29contested · 4 families support, 10 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT017190031,413 enrolled · 2012
Adjusted mean -0.72-0.95 to -0.48
NCT018093271,186 enrolled · 2013
Δ -0.40-0.59 to -0.21
NCT022730501,136 enrolled · 2014
Δ -8.90-13.3 to -4.50
NCT01126580807 enrolled · 2010
Δ -0.22-0.36 to -0.08
NCT01023581784 enrolled · 2009
Δ -0.67-0.96 to -0.37
NCT00386100688 enrolled · 2006
Δ 1.47-14.8 to 20.8
NCT01217073685 enrolled · 2010
Δ 1.00-9.80 to 13.1
NCT01890122647 enrolled · 2013
Δ -0.68-0.89 to -0.47
NCT00727857600 enrolled · 2007
Δ 0.860.51 to 1.22
NCT01958671461 enrolled · 2013
Δ -2.60-13.1 to 8.10
NCT00328172302 enrolled · 2006
Δ -0.85-1.10 to -0.59
NCT01485614200 enrolled · 2012
Δ 2.40-10.0 to 14.9

This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.

4 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

5 · Its place in the literature

Who cites it

45 citing papers in PubMed, 4 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Trial
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Review
  18. Article
  19. Article
  20. Diabetes and cancer: therapeutic implications.Cardio-oncology (London, England) · 2026
    Review
6 · The record

Corrections and comments

7 · Who and what money

Authors and funding

8 authors.

Lauren O'ConnorCancer Prevention Fellowship Program, Division of Cancer Prevention, National Cancer Institute, Rockville, MD, USA.
Maeve Bailey-WhyteSchool of Medicine, University of Limerick, Limerick, Ireland.
Manami BhattacharyaSurveillance Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, Rockville, MD, USA.ORCID 0000-0003-3116-6065
Gisela ButeraDivision of Library Services, Office of Research Services, National Institutes of Health, Bethesda, MD, USA.
Kaitlyn N Lewis HardellCancer Prevention Fellowship Program, Division of Cancer Prevention, National Cancer Institute, Rockville, MD, USA.
Andrew B SeidenbergBehavioral Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, Rockville, MD, USA.ORCID 0000-0001-5001-2067
Philip E CastleDivisions of Cancer Prevention and Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.ORCID 0000-0002-6408-5985
Holli A Loomans-KroppDivison of Cancer Prevention and Control, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA.ORCID 0000-0002-9681-8725

Funding

NIH HHSThe Ohio State University
8 · The paper itself

Abstract

The marked sentences are the ones the graph read a number from.

backgroundMetformin is among the most widely used antidiabetics medications because of its minimal toxicity, favorable safety profile, availability, and low cost. In addition to its role in diabetes management, metformin may reduce cancer risk.

methodsWe conducted a comprehensive systematic review and meta-analysis to investigate the association between metformin use and cancer risk, with evaluation by specific cancer type when possible. Applicable studies were identified in PubMed/MEDLINE, Embase, Cochrane Library, Web of Science, and Scopus from inception through March 7, 2023, with metformin use categorized as "ever" or "yes" and a cancer diagnosis as the outcome. Article quality was evaluated using National Heart, Lung, and Blood Institute guidelines, and publication bias was evaluated using the Egger test, Begg test, and funnel plots. Pooled relative risk (RR) estimates were calculated using random-effects models, and sensitivity analysis was completed through leave-one-out cross-validation.

resultsWe included 166 studies with cancer incidence information in the meta-analysis. Reduced risk for overall cancer was observed in case-control studies (RR = 0.55, 95% confidence interval [CI] = 0.30 to 0.80) and prospective cohort studies (RR = 0.65, 95% CI = 0.37 to 0.93). Metformin use was associated with reduced gastrointestinal (RR = 0.79, 95% CI = 0.73 to 0.85), urologic (RR = 0.88, 95% CI = 0.78 to 0.99), and hematologic (RR = 0.87, 95% CI = 0.75 to 0.99) cancer risk. Statistically significant publication bias was observed within the studies (Egger P < .001).

conclusionsMetformin may be associated with a decreased risk of many cancer types, but high heterogeneity and risk of publication bias limit confidence in these results. Additional studies in populations without diabetes are needed to better understand the utility of metformin in cancer prevention.

Indexed as

Hypoglycemic AgentsMetforminNeoplasmsDiabetes Mellitus, Type 2HumansIncidenceHypoglycemic AgentsMetformin

Identifiers

PMID38291943
PMCPMC10995851

What Socratic holds

Texttitle and abstract
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.