Evidence map›SGLT2 inhibitors × glycemic control›PMID 27835680›Full record

SynthesisPloS one2016

Benefits and Harms of Sodium-Glucose Co-Transporter 2 Inhibitors in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis.

Heidi Storgaard, Lise L Gluud, Cathy Bennett, Magnus F Grøndahl, Mikkel B Christensen, Filip K Knop, Tina Vilsbøll

Open access · goldFull text readMeta-AnalysisSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in PloS one, 2016. The graph read 3 numbers from its abstract, feeding 1 cell of the map: it supports the treatment in 1. Cited by 110 papers, 9 of them syntheses that pooled it.

3numbers the graph read from it
1cell of the map it votes in
110citing papers in PubMed, 9 pooled it
17.1field-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.

← favours the treatmentfavours the comparator →
-0.990 · no effect
HbA1cSGLT2-i vs placebofavours the treatment · t2dfeeds one cell of the map
Δ -0.69-0.75 to -0.62
RESULTS: Meta-analysis of 34 RCTs with 9,154 patients showed that SGLT2-i reduced HbA1c compared with placebo (mean difference -0.69%, 95% confidence interval -0.75 to -0.62%).
FeedsSGLT2 inhibitors×glycemic control
HbA1cCanagliflozin vs placebofavours the treatment · t2dfeeds one cell of the map
Δ -0.85-0.99 to -0.71
Canagliflozin was associated with the largest reduction in HbA1c (-0.85%, -0.99% to -0.71%).
FeedsSGLT2 inhibitors×glycemic control

Read, but not usablea number the graph found but could not read as for or against

HbA1cSGLT2-i vs OADcomparator not stated · t2dfeeds one cell of the map
Δ -0.20-0.28 to -0.13
Analysis of 12 RCTs found a beneficial effect of SGLT2-i on HbA1c compared with OAD (-0.20%, -0.28 to -0.13%; moderate quality evidence).
FeedsSGLT2 inhibitors×glycemic control

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×glycemic control

SupportsOpen on the map →What to test next →

40 readable studies in this cell: 81 favour the treatment, 11 find no difference, 4 favour the comparator.

Belief with this paper
0.92replicated · 70 families support, 6 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT010326294,330 enrolled · 2009
Δ 2.79-1.57 to 7.15
NCT011374742,996 enrolled · 2010
Δ -0.46-0.59 to -0.33
NCT011956622,245 enrolled · 2010
Δ -0.61-0.76 to -0.46
NCT010956661,484 enrolled · 2010
Δ -0.59-0.76 to -0.42
NCT009688121,452 enrolled · 2009
Δ -0.01-0.11 to 0.09
NCT017190031,413 enrolled · 2012
Adjusted mean -0.33-0.56 to -0.10
NCT011066771,284 enrolled · 2010
Δ -0.62-0.76 to -0.48
NCT016060071,282 enrolled · 2012
Δ -0.59-0.81 to -0.37
NCT006732311,240 enrolled · 2008
Δ -0.45-0.59 to -0.31
NCT020991101,233 enrolled · 2014
Δ -0.43-0.60 to -0.27
NCT006609071,217 enrolled · 2008
Δ 0.00-0.11 to 0.11
NCT018093271,186 enrolled · 2013
Δ -0.46-0.66 to -0.27

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

110 citing papers in PubMed, 9 syntheses or guidelines pooled it, 240 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Guideline
  5. Pooled it
  6. Pooled it
  7. Pooled it
  8. Pooled it
  9. Guideline
  10. Trial
  11. Trial
  12. Trial
  13. Trial
  14. Trial
  15. Trial
  16. Trial
  17. Trial
  18. Review
  19. Review
  20. Review

50 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

7 authors at 3 institutions in 2 countries.

Heidi StorgaardCentre for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.ORCID http://orcid.org/0000-0003-1177-2658
Lise L GluudGastrounit, Copenhagen University, Hvidovre Hospital, Hvidovre, Denmark.
Cathy BennettCentre for Technology Enabled Health Research, Coventry University, Coventry, United Kingdom.
Magnus F GrøndahlCentre for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
Mikkel B ChristensenCentre for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
Filip K KnopCentre for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
Tina VilsbøllCentre for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
University of Copenhagen · DKCoventry University · GBHvidovre Hospital · DK

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.

objectiveSodium-glucose co-transporter 2 inhibitors (SGLT2-i) are a novel drug class for the treatment of diabetes. We aimed at describing the maximal benefits and risks associated with SGLT2-i for patients with type 2 diabetes.

designSystematic review and meta-analysis. DATA SOURCES AND STUDY SELECTION: We included double-blinded, randomised controlled trials (RCTs) evaluating SGLT2-i administered in the highest approved therapeutic doses (canagliflozin 300 mg/day, dapagliflozin 10 mg/day, and empagliflozin 25 mg/day) for ≥12 weeks. Comparison groups could receive placebo or oral antidiabetic drugs (OAD) including metformin, sulphonylureas (SU), or dipeptidyl peptidase 4 inhibitors (DPP-4-i). Trials were identified through electronic databases and extensive manual searches. Primary outcomes were glycated haemoglobin A1c (HbA1c) levels, serious adverse events, death, severe hypoglycaemia, ketoacidosis and CVD. Secondary outcomes were fasting plasma glucose, body weight, blood pressure, heart rate, lipids, liver function tests, creatinine and adverse events including infections. The quality of the evidence was assessed using GRADE.

resultsMeta-analysis of 34 RCTs with 9,154 patients showed that SGLT2-i reduced HbA1c compared with placebo (mean difference -0.69%, 95% confidence interval -0.75 to -0.62%). We downgraded the evidence to 'low quality' due to variability and evidence of publication bias (P = 0.015). Canagliflozin was associated with the largest reduction in HbA1c (-0.85%, -0.99% to -0.71%). There were no differences between SGLT2-i and placebo for serious adverse events. SGLT2-i increased the risk of urinary and genital tract infections and increased serum creatinine, and exerted beneficial effects on bodyweight, blood pressure, lipids and alanine aminotransferase (moderate to low quality evidence). Analysis of 12 RCTs found a beneficial effect of SGLT2-i on HbA1c compared with OAD (-0.20%, -0.28 to -0.13%; moderate quality evidence).

conclusionThis review includes a large number of patients with type 2 diabetes and found that SGLT2-i reduces HbA1c with a notable increased risk in non-serious adverse events. The analyses may overestimate the intervention benefit due bias.

Indexed as

Sodium-Glucose Transporter 2 InhibitorsBenzhydryl CompoundsCanagliflozinDiabetes Mellitus, Type 2GlucosidesGlycated HemoglobinHumansHypoglycemic AgentsRandomized Controlled Trials as TopicSodium-Glucose Transporter 2Treatment OutcomeBenzhydryl CompoundsCanagliflozindapagliflozinempagliflozinGlucosidesGlycated HemoglobinHypoglycemic AgentsSodium-Glucose Transporter 2Sodium-Glucose Transporter 2 Inhibitors

Identifiers

PMID27835680
PMCPMC5106000
OpenAlexW2550194700

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.