Evidence map›Metformin × all-cause mortality›PMID 30045293›Full record

SynthesisMedicine2018

Association of metformin intake with bladder cancer risk and oncologic outcomes in type 2 diabetes mellitus patients: A systematic review and meta-analysis.

Jiao Hu, Jin-Bo Chen, Yu Cui, Ye-Wen Zhu, Wen-Biao Ren, Xu Zhou, Long-Fei Liu, He-Qun Chen, Xiong-Bing Zu

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

Synthesis in Medicine, 2018. The graph read 12 numbers from its abstract, feeding 2 cells 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 HR 0.70 (0.51 to 0.96) for adverse events & safety. Cited by 29 papers, 7 of them syntheses that pooled it.

12numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 7 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

All-cause mortalityan association or prognostic statement, not a treatment comparison · t2dfeeds one cell of the map
HR 0.700.51 to 0.96P = .03
A meta-analysis revealed that metformin intake was associated with an increased recurrence-free survival (HR = 0.55, 95% confidence interval [CI] = 0.35-0.88; P = .01; I = 64%), improved progression-free survival (HR = 0.70, 95% CI = 0.51-0.96; P = .03; I = 33%), and prolonged cancer-specific survival (HR = 0.57, 95% CI = 0.40-0.81; P = .002; I = 0%).
FeedsMetformin×all-cause mortality
All-cause mortalityan association or prognostic statement, not a treatment comparison · t2dfeeds one cell of the map
HR 0.570.40 to 0.81P = .002
A meta-analysis revealed that metformin intake was associated with an increased recurrence-free survival (HR = 0.55, 95% confidence interval [CI] = 0.35-0.88; P = .01; I = 64%), improved progression-free survival (HR = 0.70, 95% CI = 0.51-0.96; P = .03; I = 33%), and prolonged cancer-specific survival (HR = 0.57, 95% CI = 0.40-0.81; P = .002; I = 0%).
FeedsMetformin×all-cause mortality
Adverse events & safetyan association or prognostic statement, not a treatment comparison · t2dfeeds one cell of the map
HR 0.820.61 to 1.09P = .17
However, results demonstrated that metformin intake was not associated with a decreased incidence of bladder cancer (HR = 0.82, 95% CI = 0.61-1.09; P = .17; I = 85%) or an increased overall survival in bladder cancer patients (HR = 0.83, 95% CI = 0.47-1.44; P = .50; I = 64%).
FeedsMetformin×adverse events & safety
All-cause mortalityan association or prognostic statement, not a treatment comparison · t2dfeeds one cell of the map
HR 0.830.47 to 1.44P = .50
However, results demonstrated that metformin intake was not associated with a decreased incidence of bladder cancer (HR = 0.82, 95% CI = 0.61-1.09; P = .17; I = 85%) or an increased overall survival in bladder cancer patients (HR = 0.83, 95% CI = 0.47-1.44; P = .50; I = 64%).
FeedsMetformin×all-cause mortality
Adverse events & safetyan association or prognostic statement, not a treatment comparison · t2dfeeds one cell of the map
HR 0.820.61 to 1.09P = .17
Overall, metformin use was not associated with a decreased incidence of bladder cancer (HR = 0.82, 95% CI = 0.61-1.09; P = .17).
FeedsMetformin×adverse events & safety
Adverse events & safetyan association or prognostic statement, not a treatment comparison · t2dfeeds one cell of the map
HR 0.620.48 to 0.81P < .01
A subgroup analysis by different ethnicities demonstrated that metformin intake had a significant association with bladder cancer among Asian patients (HR = 0.62; 95% CI = 0.48-0.81; P < .01).
FeedsMetformin×adverse events & safety
All-cause mortalityan association or prognostic statement, not a treatment comparison · t2dfeeds one cell of the map
HR 0.550.35 to 0.88P = .01
A meta-analysis revealed that metformin intake was associated with an increased recurrence-free survival (HR = 0.55, 95% confidence interval [CI] = 0.35-0.88; P = .01; I = 64%), improved progression-free survival (HR = 0.70, 95% CI = 0.51-0.96; P = .03; I = 33%), and prolonged cancer-specific survival (HR = 0.57, 95% CI = 0.40-0.81; P = .002; I = 0%).
FeedsMetformin×all-cause mortality
Adverse events & safetyan association or prognostic statement, not a treatment comparison · t2dfeeds one cell of the map
HR 0.550.35 to 0.88P = .01
Overall, metformin intake was associated with an increased RFS of bladder cancer (HR = 0.55, 95% CI = 0.35-0.88; P = .01).
FeedsMetformin×adverse events & safety
Adverse events & safetyan association or prognostic statement, not a treatment comparison · t2dfeeds one cell of the map
HR 0.460.30 to 0.71P < .01
Subgroup analysis by different tumor stage demonstrated that metformin use had an increased RFS for muscle invasive bladder cancer (MIBC) (HR = 0.46; 95% CI = 0.30-0.71; P < .01), whereas such an association was not observed for non-muscle invasive bladder cancer (NMIBC) (HR = 0.65, 95% CI = 0.27-1.54; P = .33) (Fig. 3A).
FeedsMetformin×adverse events & safety
Adverse events & safetyan association or prognostic statement, not a treatment comparison · t2dfeeds one cell of the map
HR 0.570.40 to 0.81P = .002
Overall, metformin intake was associated with an increased CSS of bladder cancer (HR = 0.57, 95% CI = 0.40-0.81; P = .002) (Fig. 4B).
FeedsMetformin×adverse events & safety
Adverse events & safetyan association or prognostic statement, not a treatment comparison · t2dfeeds one cell of the map
HR 0.830.47 to 1.44P = .50
Overall, no significant association was observed between metformin use and OS of bladder cancer (HR = 0.83, 95% CI = 0.47-1.44; P = .50) (Fig. 4A).
FeedsMetformin×adverse events & safety
Adverse events & safetyan association or prognostic statement, not a treatment comparison · t2dfeeds one cell of the map
HR 0.700.51 to 0.96P = .03
Overall, metformin intake was associated with an increased PFS of bladder cancer (HR = 0.70, 95% CI = 0.51-0.96; P = .03) (Fig. 3C).
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×all-cause mortality

No readable resultOpen 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
0.50one trial · 1 family supports, 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
NCT000387272,779 enrolled · 1996
HR 0.990.79 to 1.25

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

Metformin×adverse events & safety

No readable resultOpen 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 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

29 citing papers in PubMed, 7 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update.Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists · 2022
    Guideline
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Pooled it
  8. Trial
  9. Trial
  10. Trial
  11. Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. 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

9 authors.

Jiao HuDepartment of Urology Reproductive Medicine Center, Xiangya Hospital, Central South University, Changsha, China.
Jin-Bo Chen
Yu Cui
Ye-Wen Zhu
Wen-Biao Ren
Xu Zhou
Long-Fei Liu
He-Qun Chen
Xiong-Bing Zu

Funding

No grant is acknowledged in the PubMed record.

8 · The paper itself

Abstract

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

backgroundRecent clinical trials indicated that metformin intake might play a protective role in the incidence and oncologic outcomes of various cancers. However, its protective effect on bladder cancer remains uncertain.

methodsWe performed a meta-analysis to investigate the association between metformin intake and bladder cancer risk as well as oncologic outcomes in diabetes mellitus (DM) patients. A comprehensive literature search was performed using PubMed, Embase, and the Cochrane Central Search Library in December 2017. Hazard ratio (HR) with 95% confidence interval (CI) was pooled.

resultsA total of 9 retrospective cohort studies with 1,270,179 patients were included. A meta-analysis revealed that metformin intake was associated with an increased recurrence-free survival (HR = 0.55, 95% confidence interval [CI] = 0.35-0.88; P = .01; I = 64%), improved progression-free survival (HR = 0.70, 95% CI = 0.51-0.96; P = .03; I = 33%), and prolonged cancer-specific survival (HR = 0.57, 95% CI = 0.40-0.81; P = .002; I = 0%). However, results demonstrated that metformin intake was not associated with a decreased incidence of bladder cancer (HR = 0.82, 95% CI = 0.61-1.09; P = .17; I = 85%) or an increased overall survival in bladder cancer patients (HR = 0.83, 95% CI = 0.47-1.44; P = .50; I = 64%).

conclusionThe present meta-analysis indicated that metformin intake could improve the prognosis of bladder cancer patients. Further prospective cohort studies and mechanistic studies are still required to determine the precise role of metformin in the initiation and progression of bladder cancer.

Indexed as

AgedDiabetes Mellitus, Type 2Disease-Free SurvivalDisease ProgressionFemaleHumansHypoglycemic AgentsMaleMetforminMiddle AgedPrognosisProportional Hazards ModelsRetrospective StudiesRisk FactorsUrinary Bladder NeoplasmsHypoglycemic AgentsMetformin

Identifiers

PMID30045293
PMCPMC6078654

What Socratic holds

Textfull text, public
LicenceCC BY
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.