Evidence map›Paper›PMID 40639383›Full record

Trial reportThe Lancet. Oncology2025

Metformin for patients with metastatic prostate cancer starting androgen deprivation therapy: a randomised phase 3 trial of the STAMPEDE platform protocol.

Silke Gillessen, Laura Murphy, Nicholas D James, Ashwin Sachdeva, Omar El-Taji, Hoda Abdel-Aty, Amanda I Adler, Claire Amos, Gerhardt Attard, Mohini Varughese and 44 more

Abstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Lancet. Oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 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.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · 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.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
  3. Review
  4. Review
  5. Article
  6. Review
  7. Diabetes and cancer: therapeutic implications.Cardio-oncology (London, England) · 2026
    Review
  8. Article
  9. [Less is more: dose de-escalation in early anal cancer-Clinical and functional aspects of quality of life from the PLATO-ACT4 trial].Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2025
    Article
  10. Article
4 · The record

Corrections and comments

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

5 · Who and what money

Authors and funding

54 authors.

Silke GillessenInstitute of Oncology of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland; Università della Svizzera Italiana, Faculty of Biosciences, Lugano, Switzerland; Swiss Group for Clinical Cancer Research, Bern, Switzerland. Electronic address: silke.gillessen@eoc.ch.
Laura MurphyMedical Research Council Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, University College London, London, UK.
Nicholas D JamesThe Institute of Cancer Research and The Royal Marsden Hospital, London, UK.
Ashwin SachdevaDivision of Cancer Sciences, University of Manchester, Manchester, UK; The Christie Hospital NHS Foundation Trust, Manchester, UK.
Omar El-TajiDivision of Cancer Sciences, University of Manchester, Manchester, UK; The Christie Hospital NHS Foundation Trust, Manchester, UK; Department of Urology, Salford Royal Hospital, Manchester, UK.
Hoda Abdel-AtyMedical Research Council Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, University College London, London, UK; The Institute of Cancer Research and The Royal Marsden Hospital, London, UK.
Amanda I AdlerDiabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK.
Claire AmosMedical Research Council Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, University College London, London, UK.
Gerhardt AttardUniversity College London Cancer Institute, London, UK; University College London Hospitals, London, UK.
Mohini VarugheseRoyal Devon University Hospitals NHS Foundation Trust & University of Exeter, Exeter, UK.
Joanna GaleQueen Alexandra Hospital, Portsmouth, UK.
Simon BrownOncology, Airedale General Hospital, Keighley, UK.
Narayanan SrihariRoyal Shrewsbury Hospital, Shrewsbury, UK.
Alison J BirtleRosemere Cancer Centre, Lancashire Teaching Hospitals, Preston UK; University of Manchester, Manchester, UK; University of Central Lancashire, Preston, UK.
Mick BrownDivision of Cancer Sciences, University of Manchester, Manchester, UK.
Kitty ChanMedical Research Council Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, University College London, London, UK.
Simon ChowdhuryGuy's and St Thomas' NHS Foundation Trust, London, UK.
William CrossSt James's University Hospital, Leeds, UK.
David P DearnaleyThe Institute of Cancer Research and The Royal Marsden Hospital, London, UK; Royal Marsden NHS Foundation Trust, London, UK.
Omar DinWeston Park Cancer Centre, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
Peter Dutey-MagniMedical Research Council Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, University College London, London, UK.
Duncan C GilbertMedical Research Council Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, University College London, London, UK.
Clare GilsonMedical Research Council Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, University College London, London, UK; The Institute of Cancer Research and The Royal Marsden Hospital, London, UK.
Struan GrayDivision of Cancer Sciences, University of Manchester, Manchester, UK; The Christie Hospital NHS Foundation Trust, Manchester, UK; Department of Urology, Salford Royal Hospital, Manchester, UK.
Emily GristUniversity College London Cancer Institute, London, UK.
Uschi HofmannCalderdale and Huddersfield NHS Trust, Halifax, UK.
Andrew M HudsonThe Christie Hospital NHS Foundation Trust, Manchester, UK.
Yatin JainThe Christie Hospital NHS Foundation Trust, Manchester, UK.
Ganesan JeyasangarDepartment of Oncology, Airedale General Hospital NHS Foundation Trust, Keighley, UK.
Robert JonesSchool of Cancer Sciences, University of Glasgow, Beatson West of Scotland Cancer Centre, Glasgow, UK.
Mahaz KayaniMedical Research Council Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, University College London, London, UK.
Ruth E LangleyMedical Research Council Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, University College London, London, UK.
Zafar MalikThe Clatterbridge Cancer Centre NHS Foundation Trust, Liverpool, UK.
Malcolm D MasonSchool of Medicine, Cardiff University, Cardiff, UK.
David MathesonFaculty of education Health and Wellbeing, University of Wolverhampton, Walsall, UK.
Connor McAlpineMedical Research Council Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, University College London, London, UK.
Archie MacnairMedical Research Council Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, University College London, London, UK.
Robin MillmanMedical Research Council Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, University College London, London, UK.
Claire MurphyMedical Research Council Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, University College London, London, UK.
Minal Padden-ModiMedical Research Council Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, University College London, London, UK; The Institute of Cancer Research and The Royal Marsden Hospital, London, UK.
Omi ParikhRoyal Blackburn Hospital, East Lancashire Hospitals NHS Trust, Blackburn, UK.
Chris ParkerRoyal Marsden Hospital and Institute of Cancer Research, Sutton, UK.
Hannah RushMedical Research Council Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, University College London, London, UK; Guy's and St Thomas' NHS Foundation Trust, London, UK.
Martin RussellInstitute of Cancer Sciences, University of Glasgow, Glasgow, UK.
Rajaguru SrinivasanDepartment of Oncology, Royal Devon & Exeter Hospital, Exeter, UK.
Santhanam SundarNottingham University Hospitals NHS Trust, Nottingham, UK.
Jacob S TanguayVelindre Cancer Centre, Velindre University NHS Trust, Cardiff, UK.
Fabio TurcoInstitute of Oncology of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland; Swiss Group for Clinical Cancer Research, Bern, Switzerland.
Patrick WilliamsMedical Research Council Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, University College London, London, UK.
Matthew R SydesMedical Research Council Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, University College London, London, UK.
Mahesh K B ParmarMedical Research Council Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, University College London, London, UK.
Louise C BrownMedical Research Council Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, University College London, London, UK.
Noel W ClarkeDivision of Cancer Sciences, University of Manchester, Manchester, UK; The Christie Hospital NHS Foundation Trust, Manchester, UK; Department of Urology, Salford Royal Hospital, Manchester, UK.
STAMPEDE investigators

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMetformin is a widely used anti-diabetic drug. Several studies have suggested that metformin has anticancer activity in some malignancies, including prostate cancer. Metformin might also mitigate the adverse metabolic effects of androgen-deprivation therapy (ADT). We hypothesised that metformin might improve survival in patients with metastatic hormone-sensitive prostate cancer and reduce metabolic complications associated with ADT.

methodsThe STAMPEDE multi-arm, multi-stage, randomised phase 3 trial recruited patients with high-risk locally advanced or metastatic adenocarcinoma of the prostate staged by conventional imaging with isotope bone and CT scanning. This publication reports findings for the most recent STAMPEDE research question, testing the addition of metformin to standard of care for non-diabetic (glycated haemoglobin [HbA1c] <48 mmol/mol [equivalent to <6·5%]) patients with metastatic disease with adequate renal function (glomerular filtration rate ≥45 ml/min/1·73 m

findingsBetween Sep 5, 2016, and Mar 31, 2023, 1874 patients with metastatic disease were randomly allocated to standard of care (n=938) or standard of care plus metformin (n=936). The median patient age was 69 years (IQR 63-73) and the median PSA was 84 ng/mL (24-352). 1758 (94%) of 1874 patients were newly diagnosed with metastatic disease and 116 (6%) were diagnosed with metachronous relapsing disease. 1543 (82%) of 1874 patients received ADT plus docetaxel and 52 (3%) received abiraterone, enzalutamide, or apalutamide. The median time to most recent case report form follow-up was 60 months (IQR 49-72). 473 deaths were reported in the standard of care group; median survival was 61·8 months (IQR 29·7 to not reached). There were 453 deaths in the metformin group; median survival was 67·4 months (32·5 to not reached; HR 0·91, 95% CI 0·80-1·03; p=0·15). Grade 3 or worse adverse events were reported in 487 (52%) of 938 patients in the standard of care group and 523 (57%) of 921 patients in the standard of care plus metformin group. 61 (7%) patients in the standard of care group and 84 (9%) patients in the standard of care plus metformin group reported at least one grade 3 or worse gastrointestinal adverse event; all other body systems showed no difference in grade 3 adverse events. There were six drug-related deaths in the standard of care group and one in the standard of care plus metformin group.

interpretationWe did not find significant evidence of an overall survival benefit of adding metformin to standard of care in the overall population of patients with metastatic hormone-sensitive prostate cancer. The side-effect profile of metformin was as expected and consisted mainly of diarrhoea. Adverse metabolic side-effects of ADT were significantly reduced in the metformin group compared with the standard of care group.

fundingCancer Research UK, Prostate Cancer UK, and UK Research and Innovation Medical Research Council.

Indexed as

AdenocarcinomaAndrogen AntagonistsHypoglycemic AgentsMetforminProstatic NeoplasmsAgedGlycated HemoglobinHumansMaleMiddle AgedNeoplasm MetastasisNitrilesThiohydantoinsAndrogen AntagonistsGlycated HemoglobinHypoglycemic AgentsMetforminNitrilesThiohydantoins

Identifiers

PMID40639383
PMCPMC12303861

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.