Evidence map›Metformin × adverse events & safety›PMID 31828167›Full record

SynthesisJournal of diabetes research2019

Monotherapy with Metformin versus Sulfonylureas and Risk of Cancer in Type 2 Diabetic Patients: A Systematic Review and Meta-Analysis.

Abraham Nigussie Mekuria, Yohanes Ayele, Assefa Tola, Kirubel Minsamo Mishore

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

Synthesis in Journal of diabetes research, 2019. The graph read 3 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 an association that does not count as treatment evidence, such as RR 0.74 (0.55 to 0.99) for adverse events & safety. Cited by 19 papers, 3 of them syntheses that pooled it.

3numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 3 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

Adverse events & safetyan association or prognostic statement, not a treatment comparison · t2dfeeds 2 cells of the map
RR 0.740.55 to 0.99
Obvious heterogeneity was noted, and monotherapy with metformin was associated with a lower risk of cancer incidence (unadjusted RR = 0.74, 95% CI: 0.55-0.99, CONCLUSIONS: According to this review, the monotherapy with metformin appears to be associated with a lower risk of cancer incidence than monotherapy with sulfonylurea in patients with type 2 diabetes.
FeedsMetformin×adverse events & safetySulfonylureas & glinides×adverse events & safety
Adverse events & safetycomparator not stated · t2dfeeds one cell of the map
RR 0.740.55 to 0.99p < 0.00001
Study Outcome Measures After pooling of the eight cohort studies, those that reported raw data for overall cancer incidence suggested significantly lower overall cancer incidence among T2DM patients using metformin monotherapy compared to T2DM patients using SUs as a monotherapy (RR = 0.74, 95% CI: 0.55-0.99, I 2 = 97.89%, p < 0.00001; Figure 2 ).
FeedsMetformin×adverse events & safety
Adverse events & safetyan association or prognostic statement, not a treatment comparison · t2dfeeds one cell of the map
RR 0.760.54 to 1.07p < 0.00001
After pooling of the adjusted estimates, the use of metformin was still associated with a lower risk of cancer incidence than SUs in T2DM patients (RR = 0.76, 95% CI: 0.54-1.07, I 2 = 98.12%, p < 0.00001; Figure 3 ).
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×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.

Sulfonylureas & glinides×adverse events & safety

No readable resultOpen on the map →What to test next →

8 readable studies in this cell: 1 favour the treatment, 6 find no difference, 1 favour the comparator.

Belief with this paper
0.00contested · 0 families support, 1 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the comparatorfavours the treatment →
0 · no effect
NCT017093055,570 enrolled · 2012
Estimate 0.40-0.30 to 1.30
NCT008389031,049 enrolled · 2009
Δ -0.27-0.45 to -0.09
NCT01682759751 enrolled · 2012
Δ -6.90-13.9 to 0.10
NCT02033889621 enrolled · 2013
Δ 1.50-2.10 to 5.40
NCT00770653305 enrolled · 2007
Δ 28.1-95.6 to 152
NCT0062028249 enrolled · 2008
Least squares mean 0.71-6.90 to 8.32
NCT0297347745 enrolled · 2017
Coefficient -0.00-0.16 to 0.15

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

19 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Metformin Use and Mortality in Women with Ovarian Cancer: An Updated Meta-Analysis.International journal of clinical practice · 2022 · on this map
    Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Trial
  6. The novel role ofJournal of diabetes and metabolic disorders · 2025
    Article
  7. Article
  8. Review
  9. Review
  10. Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Metformin - a new approach.Pediatric endocrinology, diabetes, and metabolism · 2021
    Review
  18. Article
  19. 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

4 authors.

Abraham Nigussie MekuriaDepartment of Pharmacology, College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia.ORCID https://orcid.org/0000-0003-0675-9862
Yohanes AyeleDepartment of Clinical Pharmacy, College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia.ORCID https://orcid.org/0000-0002-6473-7752
Assefa TolaDepartment of Epidemiology and Biostatistics, College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia.ORCID https://orcid.org/0000-0002-2155-6097
Kirubel Minsamo MishoreDepartment of Clinical Pharmacy, College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia.ORCID https://orcid.org/0000-0001-9931-1068

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.

backgroundAccumulating evidence suggests that patients with type 2 diabetes mellitus and hyperinsulinemia are at an increased risk of developing malignancies. It remains to be fully elucidated whether the use of metformin, an insulin sensitizer, and/or sulfonylureas, insulin secretagogues, affects cancer incidence in subjects with type 2 diabetes mellitus.

objectiveA systematic review and meta-analysis was performed to compare the risk of cancer incidence associated with monotherapy with metformin compared with monotherapy with sulfonylureas in type 2 diabetes mellitus patients.

methodsSearch was performed throughout MEDLINE/PubMed, EMBASE, Google Scholar, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov up until December 2018. In this meta-analysis, each raw data (unadjusted) and study-specific (adjusted) relative risks (RRs) was combined and the pooled unadjusted and adjusted RRs with the 95% CI were calculated using the random-effects model with inverse-variance weighting. Heterogeneity among the studies was evaluated using

resultsA total of 8 cohort studies were included in the meta-analysis. Obvious heterogeneity was noted, and monotherapy with metformin was associated with a lower risk of cancer incidence (unadjusted RR = 0.74, 95% CI: 0.55-0.99,

conclusionsAccording to this review, the monotherapy with metformin appears to be associated with a lower risk of cancer incidence than monotherapy with sulfonylurea in patients with type 2 diabetes. This analysis is mainly based on cohort studies, and our findings underscore the need for large-scale randomized controlled trials to establish the effect of metformin monotherapy, relative to sulfonylureas monotherapy on cancer.

Indexed as

Diabetes Mellitus, Type 2HumansHypoglycemic AgentsIncidenceMetforminNeoplasmsSulfonylurea CompoundsHypoglycemic AgentsMetforminSulfonylurea Compounds

Identifiers

PMID31828167
PMCPMC6885827

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.