Evidence map›Metformin × all-cause mortality›PMID 18458139›Full record

SynthesisDiabetes care2008

Is the combination of sulfonylureas and metformin associated with an increased risk of cardiovascular disease or all-cause mortality?: a meta-analysis of observational studies.

Ajay D Rao, Nitesh Kuhadiya, Kristi Reynolds, Vivian A Fonseca

Open access · hybridAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Diabetes care, 2008. The graph read 3 numbers from its abstract, feeding 4 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 1.43 (1.10 to 1.85) for composite end point of CVD hospitalizations or mortality (fatal or nonfatal events). Cited by 75 papers, 9 of them syntheses that pooled it.

3numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed, 9 pooled it
10.2field-weighted citation impact, top 1% of its field
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

CVD mortalitycombination therapy of sulfonylureas and metformin vs diet therapy, metformin monotherapy, or sulfonylurea monotherapyan association or prognostic statement, not a treatment comparison · ascvd, t2dfeeds 2 cells of the map
RR 1.290.73 to 2.27
RESULTS: The pooled RRs (95% CIs) of outcomes for individuals with type 2 diabetes prescribed combination therapy of sulfonylureas and metformin were 1.19 (0.88-1.62) for all-cause mortality, 1.29 (0.73-2.27) for CVD mortality, and 1.43 (1.10-1.85) for a composite end point of CVD hospitalizations or mortality (fatal or nonfatal events).
FeedsMetformin×all-cause mortalitySulfonylureas & glinides×all-cause mortality
All-cause mortalitycombination therapy of sulfonylureas and metformin vs diet therapy, metformin monotherapy, or sulfonylurea monotherapyan association or prognostic statement, not a treatment comparison · ascvd, t2dfeeds 2 cells of the map
RR 1.190.88 to 1.62
RESULTS: The pooled RRs (95% CIs) of outcomes for individuals with type 2 diabetes prescribed combination therapy of sulfonylureas and metformin were 1.19 (0.88-1.62) for all-cause mortality, 1.29 (0.73-2.27) for CVD mortality, and 1.43 (1.10-1.85) for a composite end point of CVD hospitalizations or mortality (fatal or nonfatal events).
FeedsMetformin×all-cause mortalitySulfonylureas & glinides×all-cause mortality
Composite end point of CVD hospitalizations or mortality (fatal or nonfatal events)combination therapy of sulfonylureas and metformin vs diet therapy, metformin monotherapy, or sulfonylurea monotherapyan association or prognostic statement, not a treatment comparison · ascvd, t2dfeeds 2 cells of the map
RR 1.431.10 to 1.85
RESULTS: The pooled RRs (95% CIs) of outcomes for individuals with type 2 diabetes prescribed combination therapy of sulfonylureas and metformin were 1.19 (0.88-1.62) for all-cause mortality, 1.29 (0.73-2.27) for CVD mortality, and 1.43 (1.10-1.85) for a composite end point of CVD hospitalizations or mortality (fatal or nonfatal events).
FeedsMetformin×adverse events & safetySulfonylureas & glinides×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.

Sulfonylureas & glinides×all-cause mortality

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

No other readable study in this cell yet. This paper is the evidence.

Belief with this paperNo claim has been compiled for this cell yet.

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

75 citing papers in PubMed, 9 syntheses or guidelines pooled it, 208 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Pooled it
  8. Pooled it
  9. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus.The Cochrane database of systematic reviews · 2010 · on this map
    Pooled it
  10. Trial
  11. Trial
  12. Trial
  13. Trial
  14. Trial
  15. Review
  16. Article
  17. Review
  18. Article
  19. Review
  20. Article

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

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 at 1 institution in 1 country.

Ajay D RaoDepartment of Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA.
Nitesh Kuhadiya
Kristi Reynolds
Vivian A Fonseca
Tulane University · US

Funding

TULANE COBRE: TRANSGENIC &GENE-TARGETED ANIMAL COREP20RR017659 · TULANE UNIVERSITY OF LOUISIANA · 2002 to 2005
$8.5M
NCRR NIH HHS P20 RR017659NCRR NIH HHS P20-RR17659
8 · The paper itself

Abstract

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

objectiveObservational studies assessing the association of combination therapy of metformin and sulfonylurea on all-cause and/or cardiovascular mortality in type 2 diabetes have shown conflicting results. We therefore evaluated the effects of combination therapy of sulfonylureas and metformin on the risk of all-cause mortality and cardiovascular disease (CVD) among people with type 2 diabetes. RESEARCH DESIGN AND

methodsA MEDLINE search (January 1966-July 2007) was conducted to identify observational studies that examined the association between combination therapy of sulfonylureas and metformin on risk of CVD or all-cause mortality. From 299 relevant reports, 9 were included in the meta-analysis. In these studies, combination therapy of metformin and sulfonylurea was assessed, the risk of CVD and/or mortality was reported, and adjusted relative risk (RR) or equivalent (hazard ratio and odds ratio) and corresponding variance or equivalent was reported.

resultsThe pooled RRs (95% CIs) of outcomes for individuals with type 2 diabetes prescribed combination therapy of sulfonylureas and metformin were 1.19 (0.88-1.62) for all-cause mortality, 1.29 (0.73-2.27) for CVD mortality, and 1.43 (1.10-1.85) for a composite end point of CVD hospitalizations or mortality (fatal or nonfatal events).

conclusionsThe combination therapy of metformin and sulfonylurea significantly increased the RR of the composite end point of cardiovascular hospitalization or mortality (fatal and nonfatal events) irrespective of the reference group (diet therapy, metformin monotherapy, or sulfonylurea monotherapy); however, there were no significant effects of this combination therapy on either CVD mortality or all-cause mortality alone.

Indexed as

AgedCardiovascular DiseasesDiabetes Mellitus, Type 2Diabetic AngiopathiesDrug Therapy, CombinationFemaleHumansHypoglycemic AgentsMaleMetforminMiddle AgedSulfonylurea CompoundsHypoglycemic AgentsMetforminSulfonylurea Compounds

Identifiers

PMID18458139
PMCPMC2494623
OpenAlexW2095784604

What Socratic 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 Socratic graph.