Trial reportCancer prevention research (Philadelphia, Pa.)2025

Randomized Study of Metformin and Intensive Lifestyle Intervention on Cancer Incidence over 21 Years of Follow-up in the Diabetes Prevention Program.

Brandy M Heckman-Stoddard, Jill P Crandall, Sharon L Edelstein, Philip C Prorok, Dana Dabelea, Richard Hamman, Helen P Hazuda, Edward Horton, Mary A Hoskin, Marjorie Perloff and 5 more

Abstract readClinical Trial, Phase IIIRandomized Controlled Trial
In one paragraph

Trial report in Cancer prevention research (Philadelphia, Pa.), 2025. The graph read 2 numbers from its abstract, feeding 2 cells of the map: it finds no clear difference in 2. Cited by 9 papers.

2numbers the graph read from it
2cells of the map it votes in
9citing papers in PubMed
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.

← favours the treatmentfavours the comparator →
1 · no effect
Total cancer incidencemetformin (850 mg twice daily) vs blinded placebono clear difference · t2dfeeds one cell of the map
HR 0.900.73 to 1.10
Incidence rates of cancer were 9.8, 10.5, and 10.8 per 1,000 person-years in metformin, ILS, and placebo, respectively, with a HR of 0.90 (95% confidence interval, 0.73-1.10) for metformin compared with placebo and 0.96 (95% confidence interval, 0.79-1.18) for ILS compared with placebo.
Total cancer incidenceintensive lifestyle (ILS) intervention vs blinded placebono clear difference · t2dfeeds one cell of the map
HR 0.960.79 to 1.18
Incidence rates of cancer were 9.8, 10.5, and 10.8 per 1,000 person-years in metformin, ILS, and placebo, respectively, with a HR of 0.90 (95% confidence interval, 0.73-1.10) for metformin compared with placebo and 0.96 (95% confidence interval, 0.79-1.18) for ILS compared with placebo.

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.

Diet, exercise & lifestyle×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 itThis paper is the only evidence family behind the claim. Without it there is no number.
← favours the treatmentfavours the comparator →
1 · no effect
This paper · 2025
HR 0.960.79 to 1.18

Metformin×adverse events & safety

InconclusiveOpen on the map →What to test next →

22 readable studies in this cell: 9 favour the treatment, 8 find no difference, 5 favour the comparator.

Belief with this paper
0.27contested · 4 families support, 11 contradict · against placebo
Without it
0.27This paper does not move the number.
← favours the treatmentfavours the comparator →
1 · no effect
This paper · 2025
HR 0.900.73 to 1.10
NCT02932475831 enrolled · 2017
OR 0.860.63 to 1.19
NCT02980276535 enrolled · 2017
OR 0.530.27 to 1.01
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

9 citing papers in PubMed.

  1. Trial
  2. Trial
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Review
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

15 authors.

Brandy M Heckman-Stoddard *Division of Cancer Prevention, National Cancer Institute, Rockville, Maryland.ORCID 0000-0003-1686-7154
Jill P Crandall *Division of Endocrinology, Fleischer Institute for Diabetes and Metabolism, Albert Einstein College of Medicine, Bronx, New York.ORCID 0000-0001-5576-4428
Sharon L EdelsteinBiostatistics Center, Milken Institute School of Public Health, George Washington University, Rockville, Maryland.ORCID 0000-0001-8457-4404
Philip C ProrokDivision of Cancer Prevention, National Cancer Institute, Rockville, Maryland.ORCID 0000-0002-2126-5847
Dana DabeleaDepartment of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, Colorado.ORCID 0000-0001-9514-8929
Richard HammanDepartment of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, Colorado.ORCID 0000-0003-2099-6274
Helen P HazudaUniversity of Texas Health Science Center, San Antonio, Texas.ORCID 0000-0002-7313-4160
Edward HortonJoslin Diabetes Center, Boston, Massachusetts.ORCID 0000-0002-5670-3157
Mary A HoskinDiabetes Epidemiology and Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona.ORCID 0000-0002-4964-2763
Marjorie PerloffDivision of Cancer Prevention, National Cancer Institute, Rockville, Maryland.ORCID 0000-0003-4244-8367
Anna BowersBiostatistics Center, Milken Institute School of Public Health, George Washington University, Rockville, Maryland.ORCID 0009-0006-0880-7310
William C KnowlerDiabetes Epidemiology and Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona.ORCID 0000-0002-7004-5197
Leslie G FordDivision of Cancer Prevention, National Cancer Institute, Rockville, Maryland.ORCID 0000-0003-2412-8028
Marinella TemprosaBiostatistics Center, Milken Institute School of Public Health, George Washington University, Rockville, Maryland.ORCID 0000-0002-9976-745X
DPP Research Group

Funding

PRIMARY PREVENTION TRIAL--DATA COORDINATING CENTERU01DK048489 · GEORGE WASHINGTON UNIVERSITY · 1994 to 2005
$23.7M
Post-DDP Follow-up StudyU01DK048413 · UNIVERSITY OF WASHINGTON · 1994 to 2005
$4.4M
TITLE OMITTEDU01DK048349 · YESHIVA UNIVERSITY · 1994 to 2005
$4.0M
PRIMARY PREVENTION TRIALU01DK048443 · UNIVERSITY OF SOUTHERN CALIFORNIA · 1994 to 2005
$4.0M
PRIMARY PREVENTION TRIAL (DPT-2)U01DK048397 · MASSACHUSETTS GENERAL HOSPITAL · 1994 to 2005
$3.8M
Post-DPP Follow-up StudyU01DK048485 · JOHNS HOPKINS UNIVERSITY · 1994 to 2005
$3.7M
NIDDM PRIMARY PREVENTION TRIALU01DK048412 · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 1994 to 2005
$3.6M
PRIMARY PREVENTION TRIAL (DPT-2)U01DK048339 · UNIVERSITY OF CALIFORNIA SAN DIEGO · 1994 to 2005
$3.6M
Post-DPP Follow-Up StudyU01DK048400 · WASHINGTON UNIVERSITY · 1994 to 2005
$3.6M
Post-DPP Follow-up StudyU01DK048437 · JOSLIN DIABETES CENTER · 1994 to 2005
$3.5M
NIDDM PRIMARY PREVENTION TRIAL (DPT 2)U01DK048404 · ST. LUKE'S-ROOSEVELT INST FOR HLTH SCIS · 1994 to 2005
$3.5M
Post-DPP Followup StudiesU01DK048411 · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 1994 to 2005
$3.4M
American Diabetes Association (ADA)Centers for Disease Control and Prevention (CDC)Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)Indian Health Service (IHS)Intramural NIH HHS Z99 CA999999National Cancer Institute (NCI)National Center for Research Resources (NCRR)National Eye Institute (NEI)National Heart, Lung, and Blood Institute (NHLBI)National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) U01DK048339National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) U01DK048349National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) U01DK048375National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) U01DK048377National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) U01DK048380National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) U01DK048381National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) U01DK048387National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) U01DK048397National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) U01DK048400National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) U01DK048404National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) U01DK048406National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) U01DK048407National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) U01DK048411National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) U01DK048412National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) U01DK048413National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) U01DK048434National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) U01DK048437National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) U01DK048443National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) U01DK048468National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) U01DK048489National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) U01DK048514National Institute on Aging (NIA)National Institute on Minority Health and Health Disparities (NIMHD)NIDDK NIH HHS U01 DK048339NIDDK NIH HHS U01 DK048349NIDDK NIH HHS U01 DK048375NIDDK NIH HHS U01 DK048377NIDDK NIH HHS U01 DK048380NIDDK NIH HHS U01 DK048381NIDDK NIH HHS U01 DK048387NIDDK NIH HHS U01 DK048397NIDDK NIH HHS U01 DK048400NIDDK NIH HHS U01 DK048404NIDDK NIH HHS U01 DK048406NIDDK NIH HHS U01 DK048407NIDDK NIH HHS U01 DK048411NIDDK NIH HHS U01 DK048412NIDDK NIH HHS U01 DK048413NIDDK NIH HHS U01 DK048434NIDDK NIH HHS U01 DK048437NIDDK NIH HHS U01 DK048443NIDDK NIH HHS U01 DK048468NIDDK NIH HHS U01 DK048485NIDDK NIH HHS U01 DK048489NIDDK NIH HHS U01 DK048514Office of Research on Women's Health (ORWH)U.S. Department of Veterans Affairs (VA)
8 · The paper itself

Abstract

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

Meta-analyses have reported a decrease in overall cancer incidence of approximately 10% to 40% with metformin use among individuals with diabetes. Lifestyle change could potentially reduce cancer incidence. The objective was to determine whether metformin or intensive lifestyle (ILS) intervention reduces the risk of cancer among adults at high risk of diabetes. The Diabetes Prevention Program (1996-2001) randomized 3,234 participants to ILS, metformin (850 mg twice daily), or blinded placebo. During follow-up through the Diabetes Prevention Program Outcomes Study, all participants were offered a modified lifestyle intervention, and metformin continued in an open-label metformin group. Participants reported cancer cases annually. Medical records were adjudicated for all reported events. The primary endpoint was total cancer incidence, comparing metformin versus placebo, with ILS versus placebo as a secondary objective. After a median follow-up of 21 years, 546 participants (173 metformin, 182 ILS, and 191 placebo) were diagnosed with a first incident cancer. Incidence rates of cancer were 9.8, 10.5, and 10.8 per 1,000 person-years in metformin, ILS, and placebo, respectively, with a HR of 0.90 (95% confidence interval, 0.73-1.10) for metformin compared with placebo and 0.96 (95% confidence interval, 0.79-1.18) for ILS compared with placebo. There were no differences between any treatment groups for obesity-related cancer or in sex-specific analyses. Neither assignment to metformin nor ILS reduced cancer incidence among adults at high risk of diabetes. These results may be impacted by increased nonstudy metformin usage over time due to the development of diabetes and reduced intensity of the ILS intervention over time. PREVENTION RELEVANCE: This study examines both metformin and ILS intervention as primary cancer prevention interventions in people at high risk for type 2 diabetes.

Indexed as

Diabetes Mellitus, Type 2Hypoglycemic AgentsLife StyleMetforminNeoplasmsAdultAgedFemaleFollow-Up StudiesHumansIncidenceMaleMiddle AgedRisk Reduction BehaviorHypoglycemic AgentsMetformin

Identifiers

PMID40243198
PMCPMC12213222

What Socratic holds

Texttitle and abstract
LicenceTDM
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.