Evidence map›Metformin × cardiovascular events›PMID 33043620›Full record

SynthesisDiabetes, obesity & metabolism2021

Sodium-glucose co-transporter-2 inhibitors with and without metformin: A meta-analysis of cardiovascular, kidney and mortality outcomes.

Brendon L Neuen, Clare Arnott, Vlado Perkovic, Gemma Figtree, Dick de Zeeuw, Greg Fulcher, Min Jun, Meg J Jardine, Sophia Zoungas, Carol Pollock and 3 more

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

Synthesis in Diabetes, obesity & metabolism, 2021. The graph read 4 numbers from its abstract, feeding 1 cell of the map: it . Cited by 37 papers, 5 of them syntheses that pooled it.

4numbers the graph read from it
1cell of the map it votes in
37citing papers in PubMed, 5 pooled it
6.2field-weighted citation impact, top 3% 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
Cardiovascular eventsfavours the treatment · head-to-head · ascvd, t2dfeeds one cell of the map
HR 0.740.63 to 0.87
There were also clear and separate reductions in HHF or cardiovascular death with SGLT2 inhibitors, irrespective of metformin use (HR 0.79, 95% CI 0.73-0.86 and HR 0.74, 95% CI 0.63-0.87, respectively; P-heterogeneity = 0.48), as well as for major kidney outcomes and all-cause mortality (all P-heterogeneity > 0.40).
FeedsMetformin×cardiovascular events
Cardiovascular eventsfavours the treatment · head-to-head · ascvd, t2dfeeds one cell of the map
HR 0.820.71 to 0.86
SGLT2 inhibitors reduced the risk of MACE, with and without concomitant metformin use (HR 0.93, 95% CI 0.87-1.00 and HR 0.82, 95% CI 0.71-0.86, respectively; P-heterogeneity = 0.14).
FeedsMetformin×cardiovascular events
Cardiovascular eventsno clear difference · head-to-head · ascvd, t2dfeeds one cell of the map
HR 0.930.87 to 1.00
SGLT2 inhibitors reduced the risk of MACE, with and without concomitant metformin use (HR 0.93, 95% CI 0.87-1.00 and HR 0.82, 95% CI 0.71-0.86, respectively; P-heterogeneity = 0.14).
FeedsMetformin×cardiovascular events
Cardiovascular eventsfavours the treatment · head-to-head · ascvd, t2dfeeds one cell of the map
HR 0.790.73 to 0.86
There were also clear and separate reductions in HHF or cardiovascular death with SGLT2 inhibitors, irrespective of metformin use (HR 0.79, 95% CI 0.73-0.86 and HR 0.74, 95% CI 0.63-0.87, respectively; P-heterogeneity = 0.48), as well as for major kidney outcomes and all-cause mortality (all P-heterogeneity > 0.40).
FeedsMetformin×cardiovascular events

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×cardiovascular events

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

5 readable studies in this cell: 4 favour the treatment, 1 find no difference, 0 favour the comparator.

Belief with this paper
0.50contested · 4 families support, 2 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
1 · no effect
Effects of metformin versus glipizide on cardiovascular outcomes in pa…PMID 23230096 · 2013
HR 0.540.30 to 0.90
Protective effect of metformin on myocardial injury in metabolic syndr…PMID 24335026 · 2014
HR 0.250.10 to 0.62
Comparative effect of saxagliptin and glimepiride with a composite end…PMID 30520221 · 2019
OR 1.381.05 to 1.82

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

37 citing papers in PubMed, 5 syntheses or guidelines pooled it, 75 citations in OpenAlex.

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

13 authors at 6 institutions in 3 countries.

Brendon L NeuenGeorge Institute for Global Health, UNSW Sydney, Sydney, New South Wales, Australia.ORCID 0000-0001-9276-8380
Clare ArnottGeorge Institute for Global Health, UNSW Sydney, Sydney, New South Wales, Australia.ORCID 0000-0001-9370-9913
Vlado PerkovicGeorge Institute for Global Health, UNSW Sydney, Sydney, New South Wales, Australia.
Gemma FigtreeKolling Institute, Royal North Shore Hospital and University of Sydney, Sydney, New South Wales, Australia.
Dick de ZeeuwUniversity of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
Greg FulcherRoyal North Shore Hospital, Sydney, New South Wales, Australia.
Min JunGeorge Institute for Global Health, UNSW Sydney, Sydney, New South Wales, Australia.
Meg J JardineGeorge Institute for Global Health, UNSW Sydney, Sydney, New South Wales, Australia.
Sophia ZoungasSchool of Public Health and Preventative Medicine, Monash University, Melbourne, Victoria, Australia.ORCID 0000-0003-2672-0949
Carol PollockKolling Institute, Royal North Shore Hospital and University of Sydney, Sydney, New South Wales, Australia.
Kenneth W MahaffeyStanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, Stanford, California.
Bruce NealGeorge Institute for Global Health, UNSW Sydney, Sydney, New South Wales, Australia.ORCID 0000-0002-0490-7465
Hiddo J L HeerspinkGeorge Institute for Global Health, UNSW Sydney, Sydney, New South Wales, Australia.ORCID 0000-0002-3126-3730
UNSW Sydney · AUThe University of Sydney · AUUniversity Medical Center Groningen · NLMonash University · AURoyal North Shore Hospital · AUStanford Medicine · US

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.

aimTo assess whether the effects of sodium-glucose co-transporter-2 (SGLT2) inhibitors on cardiovascular, kidney and mortality outcomes are consistent with and without concomitant metformin use. MATERIAL AND

methodsWe conducted a meta-analysis of event-driven, randomized, placebo-controlled SGLT2 inhibitor trials that reported cardiovascular, kidney or mortality outcomes by baseline metformin use. Treatment effects, reported as hazards ratios (HRs) and 95% confidence intervals (CIs), were pooled using random-effects meta-analysis. The main outcomes in this analysis were (i) major adverse cardiovascular events (MACE) and (ii) hospitalization for heart failure (HHF) or cardiovascular death.

resultsWe included six trials of four SGLT2 inhibitors that enrolled a total of 51 743 participants. Baseline metformin use varied from 21% in DAPA-HF to 82% in DECLARE-TIMI 58. SGLT2 inhibitors reduced the risk of MACE, with and without concomitant metformin use (HR 0.93, 95% CI 0.87-1.00 and HR 0.82, 95% CI 0.71-0.86, respectively; P-heterogeneity = 0.14). There were also clear and separate reductions in HHF or cardiovascular death with SGLT2 inhibitors, irrespective of metformin use (HR 0.79, 95% CI 0.73-0.86 and HR 0.74, 95% CI 0.63-0.87, respectively; P-heterogeneity = 0.48), as well as for major kidney outcomes and all-cause mortality (all P-heterogeneity > 0.40).

conclusionTreatment with SGLT2 inhibitors results in clear and consistent reductions in cardiovascular, kidney and mortality outcomes regardless of whether patients are receiving or not receiving metformin.

Indexed as

Cardiovascular DiseasesDiabetes Mellitus, Type 2MetforminSodium-Glucose Transporter 2 InhibitorsSymportersGlucoseHumansKidneySodiumGlucoseMetforminSodiumSodium-Glucose Transporter 2 InhibitorsSymporterscardiovascular diseaseclinical trialdiabetic nephropathyheart failuremeta-analysisSGLT2 inhibitor

Identifiers

PMID33043620
PMCPMC7821162
OpenAlexW3092315395

What Socratic holds

Texttitle and abstract
LicenceCC BY-NC
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.