Evidence map›SGLT2 inhibitors × cardiovascular events›PMID 29938883›Full record

SynthesisDiabetes, obesity & metabolism2018

Comparative effectiveness of canagliflozin, SGLT2 inhibitors and non-SGLT2 inhibitors on the risk of hospitalization for heart failure and amputation in patients with type 2 diabetes mellitus: A real-world meta-analysis of 4 observational databases (OBSERVE-4D).

Patrick B Ryan, John B Buse, Martijn J Schuemie, Frank DeFalco, Zhong Yuan, Paul E Stang, Jesse A Berlin, Norman Rosenthal

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

Synthesis in Diabetes, obesity & metabolism, 2018. The graph read 3 numbers from its abstract, feeding 1 cell 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 HR 0.39 (0.26 to 0.60) for HHF. Cited by 81 papers, 8 of them syntheses that pooled it.

3numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed, 8 pooled it
21.0field-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

HHFcanagliflozin vs non-SGLT2ian association or prognostic statement, not a treatment comparison · t2d, heart_failurefeeds one cell of the map
HR 0.390.26 to 0.60
RESULTS: Across the 4 databases (142 800 new users of canagliflozin, 110 897 new users of other SGLT2i, 460 885 new users of non-SGLT2i), the meta-analytic hazard ratio estimate for HHF with canagliflozin vs non-SGLT2i was 0.39 (95% CI, 0.26-0.60) in the on-treatment analysis.
FeedsSGLT2 inhibitors×cardiovascular events
BKLE amputationcanagliflozin vs non-SGLT2ian association or prognostic statement, not a treatment comparison · t2d, heart_failurefeeds one cell of the map
HR 1.010.93 to 1.10
The estimate for BKLE amputation with canagliflozin vs non-SGLT2i was 0.75 (95% CI, 0.40-1.41) in the on-treatment analysis and 1.01 (95% CI, 0.93-1.10) in the intent-to-treat analysis.
FeedsSGLT2 inhibitors×cardiovascular events
BKLE amputationcanagliflozin vs non-SGLT2ian association or prognostic statement, not a treatment comparison · t2d, heart_failurefeeds one cell of the map
HR 0.750.40 to 1.41
The estimate for BKLE amputation with canagliflozin vs non-SGLT2i was 0.75 (95% CI, 0.40-1.41) in the on-treatment analysis and 1.01 (95% CI, 0.93-1.10) in the intent-to-treat analysis.
FeedsSGLT2 inhibitors×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.

SGLT2 inhibitors×cardiovascular events

No readable resultOpen 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.

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

81 citing papers in PubMed, 8 syntheses or guidelines pooled it, 203 citations in OpenAlex.

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

6 · The record

Corrections and comments

7 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

Patrick B RyanJanssen Research & Development, LLC, Titusville, New Jersey.ORCID 0000-0002-9727-2138
John B BuseUniversity of North Carolina School of Medicine, Department of Medicine, Chapel Hill, North Carolina.ORCID 0000-0002-9723-3876
Martijn J SchuemieJanssen Research & Development, LLC, Titusville, New Jersey.ORCID 0000-0002-0817-5361
Frank DeFalcoJanssen Research & Development, LLC, Raritan, New Jersey.
Zhong YuanJanssen Research & Development, LLC, Titusville, New Jersey.ORCID 0000-0002-5824-2040
Paul E StangJanssen Research & Development, LLC, Titusville, New Jersey.ORCID 0000-0002-9528-9657
Jesse A BerlinJohnson & Johnson, Titusville, New Jersey.ORCID 0000-0002-9810-745X
Norman RosenthalJanssen Research & Development, LLC, Raritan, New Jersey.
Janssen (United States) · USJohnson & Johnson (United States) · USUniversity of North Carolina at Chapel Hill · US

Funding

Re-Entry Supplement: Investigation of Oral Microbial Enzymes for the Detection and Treatment of Periodontal DiseaseUL1TR002489 · NCATS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BUSE, JOHN BERNARD, SHAHEEN, NICHOLAS J · 2018 to 2022
$48.6M
NCATS NIH HHS UL1 TR002489
8 · The paper itself

Abstract

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

aimsSodium glucose co-transporter 2 inhibitors (SGLT2i) are indicated for treatment of type 2 diabetes mellitus (T2DM); some SGLT2i have reported cardiovascular benefit, and some have reported risk of below-knee lower extremity (BKLE) amputation. This study examined the real-world comparative effectiveness within the SGLT2i class and compared with non-SGLT2i antihyperglycaemic agents. MATERIALS AND

methodsData from 4 large US administrative claims databases were used to characterize risk and provide population-level estimates of canagliflozin's effects on hospitalization for heart failure (HHF) and BKLE amputation vs other SGLT2i and non-SGLT2i in T2DM patients. Comparative analyses using a propensity score-adjusted new-user cohort design examined relative hazards of outcomes across all new users and a subpopulation with established cardiovascular disease.

resultsAcross the 4 databases (142 800 new users of canagliflozin, 110 897 new users of other SGLT2i, 460 885 new users of non-SGLT2i), the meta-analytic hazard ratio estimate for HHF with canagliflozin vs non-SGLT2i was 0.39 (95% CI, 0.26-0.60) in the on-treatment analysis. The estimate for BKLE amputation with canagliflozin vs non-SGLT2i was 0.75 (95% CI, 0.40-1.41) in the on-treatment analysis and 1.01 (95% CI, 0.93-1.10) in the intent-to-treat analysis. Effects in the subpopulation with established cardiovascular disease were similar for both outcomes. No consistent differences were observed between canagliflozin and other SGLT2i.

conclusionsIn this large comprehensive analysis, canagliflozin and other SGLT2i demonstrated HHF benefits consistent with clinical trial data, but showed no increased risk of BKLE amputation vs non-SGLT2i. HHF and BKLE amputation results were similar in the subpopulation with established cardiovascular disease. This study helps further characterize the potential benefits and harms of SGLT2i in routine clinical practice to complement evidence from clinical trials and prior observational studies.

Indexed as

Diabetes Mellitus, Type 2Heart FailureAdolescentAdultAgedAged, 80 and overAmputation, SurgicalCanagliflozinDatabases as TopicDiabetic AngiopathiesDiabetic FootFemaleHospitalizationHumansMaleMiddle AgedCanagliflozinSodium-Glucose Transporter 2 InhibitorsSGLT2 inhibitortype 2 diabetes

Identifiers

PMID29938883
PMCPMC6220807
OpenAlexW2810458929

What OpenQuestion 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 OpenQuestion graph.