Evidence map›Paper›PMID 23173135›Full record

ReviewDiabetes care2012

Metformin and the risk of cancer: time-related biases in observational studies.

Samy Suissa, Laurent Azoulay

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Diabetes care, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 253 papers, 19 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
253citing papers in PubMed, 19 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

253 citing papers in PubMed, 19 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. The effect of metformin on gastric cancer in patients with type 2 diabetes: a systematic review and meta-analysis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2020 · on this map
    Pooled it
  6. Metformin and colorectal cancer: a systematic review, meta-analysis and meta-regression.International journal of colorectal disease · 2020 · on this map
    Pooled it
  7. Pooled it
  8. Pooled it
  9. Pooled it
  10. Pooled it
  11. Pooled it
  12. Pooled it
  13. Pooled it
  14. Pooled it
  15. Metformin as an adjuvant treatment for cancer: a systematic review and meta-analysis.Annals of oncology : official journal of the European Society for Medical Oncology · 2016
    Pooled it
  16. Renin-angiotensin system blockade for the risk of cancer and death.Journal of the renin-angiotensin-aldosterone system : JRAAS · 2016
    Pooled it
  17. Pooled it
  18. Pooled it
  19. Pooled it
  20. Trial

193 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

2 authors.

Samy SuissaCentre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Canada. samy.suissa@mcgill.ca
Laurent Azoulay

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveTime-related biases in observational studies of drug effects have been described extensively in different therapeutic areas but less so in diabetes. Immortal time bias, time-window bias, and time-lag bias all tend to greatly exaggerate the benefits observed with a drug. RESEARCH DESIGN AND

methodsThese time-related biases are described and shown to be prominent in observational studies that have associated metformin with impressive reductions in the incidence of and mortality from cancer. As a consequence, metformin received much attention as a potential anticancer agent; these observational studies sparked the conduction of randomized, controlled trials of metformin as cancer treatment. However, the spectacular effects reported in these studies are compatible with time-related biases.

resultsWe found that 13 observational studies suffered from immortal time bias; 9 studies had not considered time-window bias, whereas other studies did not consider inherent time-lagging issues when comparing the first-line treatment metformin with second- or third-line treatments. These studies, subject to time-related biases that are avoidable with proper study design and data analysis, led to illusory extraordinarily significant effects, with reductions in cancer risk with metformin ranging from 20 to 94%. Three studies that avoided these biases reported no effect of metformin use on cancer incidence.

conclusionsAlthough observational studies are important to better understand the effects of drugs, their proper design and analysis is essential to avoid major time-related biases. With respect to metformin, the scientific evidence of its potential beneficial effects on cancer would need to be reassessed critically before embarking on further long and expensive trials.

Indexed as

AnimalsDiabetes Mellitus, Type 2HumansHypoglycemic AgentsMetforminNeoplasmsHypoglycemic AgentsMetformin

Identifiers

PMID23173135
PMCPMC3507580

What OpenQuestion holds

Texttitle and abstract
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 OpenQuestion graph.