Trial reportJNCI cancer spectrum2023

Association of metformin, aspirin, and cancer incidence with mortality risk in adults with diabetes.

Suzanne G Orchard, Jessica E Lockery, Jonathan C Broder, Michael E Ernst, Sara Espinoza, Peter Gibbs, Rory Wolfe, Galina Polekhina, Sophia Zoungas, Holli A Loomans-Kropp and 2 more

Registry-linked trialOpen access · goldFull text readRandomized Controlled Trial
In one paragraph

Trial report in JNCI cancer spectrum, 2023. The graph read 4 numbers from its abstract, feeding 2 cells of the map: it finds no clear difference in 1. It also reports an association that does not count as treatment evidence, such as HR 0.68 (0.51 to 0.90) for cancer incidence. It is linked to trial NCT01038583 (Aspirin in Reducing Events in the Elderly), which is not on this map. Cited by 11 papers, 2 of them syntheses that pooled it.

4numbers the graph read from it
1cell of the map it votes in
11citing papers in PubMed, 2 pooled it
2.3field-weighted citation impact, top 12% of its field
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.

← favours the treatmentfavours the comparator →
241 · no effect
Cancer incidenceaspirin vs placebo, in metformin usersno clear difference · t2dfeeds one cell of the map
HR 1.110.75 to 1.64
Metformin users randomized to aspirin had greater risk of cancer mortality compared with placebo (HR = 2.53, 95% CI = 1.18 to 5.43), but no effect was seen for cancer incidence (HR = 1.11, 95% CI = 0.75 to 1.64).
Cancer mortalityaspirin vs placebo, in metformin usersfavours the comparator · t2dfeeds one cell of the map
HR 2.531.18 to 5.43
Metformin users randomized to aspirin had greater risk of cancer mortality compared with placebo (HR = 2.53, 95% CI = 1.18 to 5.43), but no effect was seen for cancer incidence (HR = 1.11, 95% CI = 0.75 to 1.64).

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

Cancer incidencemetformin vs no metforminan association or prognostic statement, not a treatment comparison · t2dfeeds one cell of the map
HR 0.680.51 to 0.90
Metformin was associated with a reduced cancer incidence risk (adjusted hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.51 to 0.90), but no conclusive benefit for cancer mortality (adjusted HR = 0.72, 95% CI = 0.43 to 1.19).
Cancer mortalitymetformin vs no metforminan association or prognostic statement, not a treatment comparison · t2dfeeds one cell of the map
HR 0.720.43 to 1.19
Metformin was associated with a reduced cancer incidence risk (adjusted hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.51 to 0.90), but no conclusive benefit for cancer mortality (adjusted HR = 0.72, 95% CI = 0.43 to 1.19).

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.

Antiplatelet & anticoagulant×adverse events & safety

InconclusiveOpen on the map →What to test next →

1 readable study in this cell: 0 favour the treatment, 1 find no difference, 0 favour the comparator.

Belief with this paper
0.25no deciding trial · 0 families support, 0 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
1 · no effect
This paper · 2023
HR 1.110.75 to 1.64

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.

NCT01038583 unknown statusnot on this map

Aspirin in Reducing Events in the Elderly

TypeobservationalSponsorHennepin Healthcare Research InstituteRan2010 to 2024Enrolled19,114ConditionsFunctional Disability, Dementia, Heart Disease, StrokeArms100 mg enteric-coated aspirin, Placebo
5 · Its place in the literature

Who cites it

11 citing papers in PubMed, 2 syntheses or guidelines pooled it, 15 citations in OpenAlex.

  1. Pooled it
  2. Association of metformin use and cancer incidence: a systematic review and meta-analysis.Journal of the National Cancer Institute · 2024 · on this map
    Pooled it
  3. Review
  4. Article
  5. Article
  6. Observational
  7. Article
  8. Article
  9. Metformin: A Dual-Role Player in Cancer Treatment and Prevention.International journal of molecular sciences · 2024
    Review
  10. Article
  11. Article
6 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

7 · Who and what money

Authors and funding

12 authors at 6 institutions in 2 countries.

Suzanne G OrchardSchool of Public Health and Preventive Medicine, Monash University, Melbourne,VIC, Australia.ORCID 0000-0003-0211-3183
Jessica E LockerySchool of Public Health and Preventive Medicine, Monash University, Melbourne,VIC, Australia.ORCID 0000-0001-6664-1239
Jonathan C BroderSchool of Public Health and Preventive Medicine, Monash University, Melbourne,VIC, Australia.
Michael E ErnstDepartment of Pharmacy Practice and Science, College of Pharmacy and Department of Family Medicine, Carver College of Medicine, The University of Iowa, Iowa City, IA, USA.ORCID 0000-0003-0267-4888
Sara EspinozaDivision of Geriatrics, Gerontology and Palliative Medicine, Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, and Geriatrics Research, Education and Clinical Center, South Texas Veterans Health Care System, San Antonio, TX, USA.
Peter GibbsThe Walter & Eliza Hall Institute of Medical Research, Royal Parade, Parkville, Melbourne, VIC, Australia.
Rory WolfeSchool of Public Health and Preventive Medicine, Monash University, Melbourne,VIC, Australia.
Galina PolekhinaSchool of Public Health and Preventive Medicine, Monash University, Melbourne,VIC, Australia.ORCID 0000-0001-9535-9291
Sophia ZoungasSchool of Public Health and Preventive Medicine, Monash University, Melbourne,VIC, Australia.
Holli A Loomans-KroppDepartment of Internal Medicine, Division of Cancer Prevention and Control, Ohio State University, Columbus, OH, USA.ORCID 0000-0002-9681-8725
Robyn L WoodsSchool of Public Health and Preventive Medicine, Monash University, Melbourne,VIC, Australia.
ASPREE Investigator Group
Monash University · AUThe Ohio State University · USThe University of Texas Health Science Center at San Antonio · USNational Cancer Institute · USUniversity of Iowa · USWalter and Eliza Hall Institute of Medical Research · AU

Funding

Research Education CoreP30AG024824 · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2004 to 2025
$4.4M
NIA NIH HHS P30 AG024824NIA NIH HHS U01 AG029824NIA NIH HHS U19 AG062682
8 · The paper itself

Abstract

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

backgroundMetformin and aspirin are commonly co-prescribed to people with diabetes. Metformin may prevent cancer, but in older people (over 70 years), aspirin has been found to increase cancer mortality. This study examined whether metformin reduces cancer mortality and incidence in older people with diabetes; it used randomization to 100 mg aspirin or placebo in the ASPirin in Reducing Events in the Elderly (ASPREE) trial to quantify aspirin's impact on metformin users.

methodsAnalysis included community-dwelling ASPREE participants (aged ≥70 years, or ≥65 years for members of US minority populations) with diabetes. Diabetes was defined as a fasting blood glucose level greater than 125 mg/dL, self-report of diabetes, or antidiabetic medication use. Cox proportional hazards regression models were used to analyze the association of metformin and a metformin-aspirin interaction with cancer incidence and mortality, with adjustment for confounders.

resultsOf 2045 participants with diabetes at enrollment, 965 were concurrently using metformin. Metformin was associated with a reduced cancer incidence risk (adjusted hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.51 to 0.90), but no conclusive benefit for cancer mortality (adjusted HR = 0.72, 95% CI = 0.43 to 1.19). Metformin users randomized to aspirin had greater risk of cancer mortality compared with placebo (HR = 2.53, 95% CI = 1.18 to 5.43), but no effect was seen for cancer incidence (HR = 1.11, 95% CI = 0.75 to 1.64). The possible effect modification of aspirin on cancer mortality, however, was not statistically significant (interaction P = .11).

conclusionsIn community-dwelling older adults with diabetes, metformin use was associated with reduced cancer incidence. Increased cancer mortality risk in metformin users randomized to aspirin warrants further investigation. ASPREE

trial registrationClinicalTrials.gov ID NCT01038583.

Indexed as

Diabetes Mellitus, Type 2MetforminNeoplasmsAgedAspirinHumansIncidenceAspirinMetformin

Identifiers

PMID36857596
PMCPMC10042437
OpenAlexW4322730686

What Socratic holds

Textfull text, public
LicenceCC BY
measurements read35
identifiers read1
Read underepoch 390

Registered trials

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.