SynthesisJournal of the American Heart Association2021

Sodium-Glucose Cotransporter 2 Inhibitors, All-Cause Mortality, and Cardiovascular Outcomes in Adults with Type 2 Diabetes: A Bayesian Meta-Analysis and Meta-Regression.

Ayodele Odutayo, Bruno R da Costa, Tiago V Pereira, Vinay Garg, Samir Iskander, Fatimah Roble, Rahim Lalji, Cesar A Hincapié, Aquila Akingbade, Myanca Rodrigues and 8 more

Open access · goldAbstract readMeta-Analysis
In one paragraph

Synthesis in Journal of the American Heart Association, 2021. The graph read 5 numbers from its abstract, feeding 2 cells of the map: it finds no clear difference in 2. Cited by 18 papers, 3 of them syntheses that pooled it.

5numbers the graph read from it
2cells of the map it votes in
18citing papers in PubMed, 3 pooled it
2.8field-weighted citation impact, top 8% 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.

← favours the treatmentfavours the comparator →
1 · no effect
All-cause mortalityno clear difference · against placebo · t2d, ascvdfeeds one cell of the map
RR 0.860.69 to 1.05
Empagliflozin, canagliflozin, and dapagliflozin reduced the incidence of all-cause mortality (empagliflozin: rate ratio [RR], 0.79; 95% credibility interval [CrI], 0.63-0.97; canagliflozin: RR, 0.86; 95% CrI, 0.69-1.05; dapagliflozin: RR, 0.86; 95% CrI, 0.72-1.01) and cardiovascular mortality (empagliflozin: RR, 0.78; 95% CrI, 0.61-1.00; canagliflozin: RR, 0.83; 95% CrI, 0.63-1.05; dapagliflozin: RR, 0.88; 95% CrI, 0.71-1.08), with a 90.1% to 98.7% probability for the true RR to be <1.00 for both outcomes.
Cardiovascular eventsno clear difference · against placebo · t2d, ascvdfeeds one cell of the map
RR 0.830.63 to 1.05
Empagliflozin, canagliflozin, and dapagliflozin reduced the incidence of all-cause mortality (empagliflozin: rate ratio [RR], 0.79; 95% credibility interval [CrI], 0.63-0.97; canagliflozin: RR, 0.86; 95% CrI, 0.69-1.05; dapagliflozin: RR, 0.86; 95% CrI, 0.72-1.01) and cardiovascular mortality (empagliflozin: RR, 0.78; 95% CrI, 0.61-1.00; canagliflozin: RR, 0.83; 95% CrI, 0.63-1.05; dapagliflozin: RR, 0.88; 95% CrI, 0.71-1.08), with a 90.1% to 98.7% probability for the true RR to be <1.00 for both outcomes.
Cardiovascular eventsno clear difference · against placebo · t2d, ascvdfeeds one cell of the map
RR 0.780.61 to 1.00
Empagliflozin, canagliflozin, and dapagliflozin reduced the incidence of all-cause mortality (empagliflozin: rate ratio [RR], 0.79; 95% credibility interval [CrI], 0.63-0.97; canagliflozin: RR, 0.86; 95% CrI, 0.69-1.05; dapagliflozin: RR, 0.86; 95% CrI, 0.72-1.01) and cardiovascular mortality (empagliflozin: RR, 0.78; 95% CrI, 0.61-1.00; canagliflozin: RR, 0.83; 95% CrI, 0.63-1.05; dapagliflozin: RR, 0.88; 95% CrI, 0.71-1.08), with a 90.1% to 98.7% probability for the true RR to be <1.00 for both outcomes.
All-cause mortalityno clear difference · against placebo · t2d, ascvdfeeds one cell of the map
RR 0.860.72 to 1.01
Empagliflozin, canagliflozin, and dapagliflozin reduced the incidence of all-cause mortality (empagliflozin: rate ratio [RR], 0.79; 95% credibility interval [CrI], 0.63-0.97; canagliflozin: RR, 0.86; 95% CrI, 0.69-1.05; dapagliflozin: RR, 0.86; 95% CrI, 0.72-1.01) and cardiovascular mortality (empagliflozin: RR, 0.78; 95% CrI, 0.61-1.00; canagliflozin: RR, 0.83; 95% CrI, 0.63-1.05; dapagliflozin: RR, 0.88; 95% CrI, 0.71-1.08), with a 90.1% to 98.7% probability for the true RR to be <1.00 for both outcomes.
Cardiovascular eventsno clear difference · against placebo · t2d, ascvdfeeds one cell of the map
RR 0.880.71 to 1.08
Empagliflozin, canagliflozin, and dapagliflozin reduced the incidence of all-cause mortality (empagliflozin: rate ratio [RR], 0.79; 95% credibility interval [CrI], 0.63-0.97; canagliflozin: RR, 0.86; 95% CrI, 0.69-1.05; dapagliflozin: RR, 0.86; 95% CrI, 0.72-1.01) and cardiovascular mortality (empagliflozin: RR, 0.78; 95% CrI, 0.61-1.00; canagliflozin: RR, 0.83; 95% CrI, 0.63-1.05; dapagliflozin: RR, 0.88; 95% CrI, 0.71-1.08), with a 90.1% to 98.7% probability for the true RR to be <1.00 for both outcomes.

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.

SGLT2 inhibitors×cardiovascular events

InconclusiveOpen on the map →What to test next →

22 readable studies in this cell: 9 favour the treatment, 11 find no difference, 2 favour the comparator.

Belief with this paper
0.50contested · 9 families support, 6 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the comparatorfavours the treatment →
1 · no effect
NCT0546531762,197 enrolled · 2022
HR 0.750.65 to 0.86
NCT0399313226,774 enrolled · 2018
HR 1.010.91 to 1.11
NCT0173053417,190 enrolled · 2013
HR 0.930.84 to 1.03
NCT0493781616,746 enrolled · 2021
HR 1.000.83 to 1.20
NCT045096746,522 enrolled · 2020
HR 0.900.76 to 1.06
NCT036192136,263 enrolled · 2018
HR 0.820.73 to 0.92
NCT030579515,988 enrolled · 2017
HR 0.790.69 to 0.90
NCT019897545,813 enrolled · 2014
HR 0.720.55 to 0.94
NCT020657914,401 enrolled · 2014
HR 0.700.59 to 0.82
NCT010326294,330 enrolled · 2009
HR 0.930.78 to 1.12
NCT045647424,017 enrolled · 2020
Win Ratio (WR) 1.341.20 to 1.50
NCT030579773,730 enrolled · 2017
HR 0.750.65 to 0.86

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

SGLT2 inhibitors×all-cause mortality

InconclusiveOpen on the map →What to test next →

13 readable studies in this cell: 5 favour the treatment, 6 find no difference, 2 favour the comparator.

Belief with this paper
0.50contested · 5 families support, 4 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the comparatorfavours the treatment →
1 · no effect
NCT0546531762,197 enrolled · 2022
HR 0.750.65 to 0.86
NCT0399313226,774 enrolled · 2018
HR 0.990.83 to 1.18
NCT0173053417,190 enrolled · 2013
HR 0.930.84 to 1.03
NCT045096746,522 enrolled · 2020
HR 0.900.76 to 1.06
NCT036192136,263 enrolled · 2018
HR 0.820.73 to 0.92
NCT030579515,988 enrolled · 2017
HR 0.790.69 to 0.90
NCT019897545,813 enrolled · 2014
HR 0.720.55 to 0.94
NCT020657914,401 enrolled · 2014
HR 0.700.59 to 0.82
NCT010326294,330 enrolled · 2009
HR 0.930.78 to 1.12
NCT030579773,730 enrolled · 2017
HR 0.750.65 to 0.86
NCT043636972,401 enrolled · 2020
HR 0.860.68 to 1.08
NCT04157751530 enrolled · 2020
Stratified Win Ratio 1.361.09 to 1.68

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

18 citing papers in PubMed, 3 syntheses or guidelines pooled it, 26 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Observational
  11. Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Review
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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

18 authors at 7 institutions in 4 countries.

Ayodele OdutayoDepartment of Medicine and Institute of Health Policy, Management and Evaluation Applied Health Research Centre (AHRC) Li Ka Shing Knowledge Institute of St. Michael's HospitalUniversity of Toronto Canada.
Bruno R da CostaDepartment of Medicine and Institute of Health Policy, Management and Evaluation Applied Health Research Centre (AHRC) Li Ka Shing Knowledge Institute of St. Michael's HospitalUniversity of Toronto Canada.
Tiago V PereiraDepartment of Medicine and Institute of Health Policy, Management and Evaluation Applied Health Research Centre (AHRC) Li Ka Shing Knowledge Institute of St. Michael's HospitalUniversity of Toronto Canada.
Vinay GargFaculty of Medicine Department of Medicine University of Toronto Ontario Canada.
Samir IskanderDepartment of Medicine and Institute of Health Policy, Management and Evaluation Applied Health Research Centre (AHRC) Li Ka Shing Knowledge Institute of St. Michael's HospitalUniversity of Toronto Canada.
Fatimah RobleFaculty of Medicine Department of Medicine University of Toronto Ontario Canada.
Rahim LaljiDepartment of Chiropractic Medicine Faculty of Medicine University of Zurich and Balgrist University Hospital Zurich Switzerland.ORCID 0000-0002-7129-2544
Cesar A HincapiéDepartment of Medicine and Institute of Health Policy, Management and Evaluation Applied Health Research Centre (AHRC) Li Ka Shing Knowledge Institute of St. Michael's HospitalUniversity of Toronto Canada.ORCID 0000-0002-7257-8122
Aquila AkingbadeFaculty of Medicine Queen's University Kingston Ontario Canada.
Myanca RodriguesHealth Research Methodology Graduate Program Department of Health Research Methods, Evidence & Impact Faculty of Health Sciences McMaster University Hamilton Ontario Canada.ORCID 0000-0001-7953-773X
Arnav AgarwalFaculty of Medicine Department of Medicine University of Toronto Ontario Canada.
Bishoy LawendyFaculty of Medicine Department of Medicine University of Toronto Ontario Canada.ORCID 0000-0002-0447-3871
Pakeezah SaadatDepartment of Medicine and Institute of Health Policy, Management and Evaluation Applied Health Research Centre (AHRC) Li Ka Shing Knowledge Institute of St. Michael's HospitalUniversity of Toronto Canada.ORCID 0000-0001-5902-8962
Jacob A UdellFaculty of Medicine Department of Medicine University of Toronto Ontario Canada.ORCID 0000-0001-7402-9584
Francesco CosentinoCardiology Unit Department of Medicine Solna Karolinska Institute &Karolinska University Hospital Stockholm Sweden.ORCID 0000-0002-6967-5685
Peter J GrantLeeds Institute of Cardiovascular and Metabolic Medicine University of Leeds/Leeds Teaching Hospitals NHS TrustLIGHT Laboratories Leeds UK.
Subodh VermaDepartments of Surgery, and Pharmacology and Toxicology University of Toronto Ontario Canada.
Peter JüniDepartment of Medicine and Institute of Health Policy, Management and Evaluation Applied Health Research Centre (AHRC) Li Ka Shing Knowledge Institute of St. Michael's HospitalUniversity of Toronto Canada.ORCID 0000-0002-5985-0670
St. Michael's Hospital · CAUniversity of Toronto · CAImpact · CAKarolinska University Hospital · SEQueen's University · CAUniversity of Leeds · GBUniversity of Zurich · CH

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.

Background This study aimed to assess the effectiveness of sodium-glucose cotransporter 2 inhibitors in reducing the incidence of mortality and cardiovascular outcomes in adults with type 2 diabetes. Methods and Results We conducted a Bayesian meta-analysis of randomized controlled trials comparing sodium-glucose cotransporter 2 inhibitors with placebo. We used meta-regression to examine the association between treatment effects and control group event rates as measures of cardiovascular baseline risk. Fifty-three randomized controlled trials were included in our synthesis. Empagliflozin, canagliflozin, and dapagliflozin reduced the incidence of all-cause mortality (empagliflozin: rate ratio [RR], 0.79; 95% credibility interval [CrI], 0.63-0.97; canagliflozin: RR, 0.86; 95% CrI, 0.69-1.05; dapagliflozin: RR, 0.86; 95% CrI, 0.72-1.01) and cardiovascular mortality (empagliflozin: RR, 0.78; 95% CrI, 0.61-1.00; canagliflozin: RR, 0.83; 95% CrI, 0.63-1.05; dapagliflozin: RR, 0.88; 95% CrI, 0.71-1.08), with a 90.1% to 98.7% probability for the true RR to be <1.00 for both outcomes. There was little evidence for ertugliflozin and sotagliflozin versus placebo for reducing all-cause and cardiovascular mortality. There was no association between treatment effects for all-cause and cardiovascular mortality and the control group event rates. There was evidence for a reduction in the incidence of heart failure for empagliflozin, canagliflozin, dapagliflozin, and ertugliflozin versus placebo (probability RR <1.00 of ≥99.3%) and weaker, albeit positive, evidence for acute myocardial infarction for the first 3 agents (probability RR <1.00 of 89.0%-95.2%). There was little evidence of any agent except canagliflozin for reducing the incidence of stroke. Conclusions Empagliflozin, canagliflozin, and dapagliflozin reduced the incidence of all-cause and cardiovascular mortality versus placebo. Treatment effects of sodium-glucose cotransporter 2 inhibitors versus placebo do not vary by baseline risk.

Indexed as

Diabetes Mellitus, Type 2StrokeBayes TheoremCanagliflozinGlucoseHumansSodiumCanagliflozinGlucoseSodiumheart failureischemic strokemeta‐analysismyocardial infarctiontype 2 diabetes

Identifiers

PMID34514812
PMCPMC8649541
OpenAlexW3199553988

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.