Evidence mapPaperPMID 34463409Full record

Trial reportDiabetes, obesity & metabolism2021

Effects of empagliflozin on insulin initiation or intensification in patients with type 2 diabetes and cardiovascular disease: Findings from the EMPA-REG OUTCOME trial.

Muthiah Vaduganathan, Silvio E Inzucchi, Naveed Sattar, David H Fitchett, Anne Pernille Ofstad, Martina Brueckmann, Jyothis T George, Subodh Verma, Michaela Mattheus, Christoph Wanner and 2 more

Open access · hybridAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Diabetes, obesity & metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.6field-weighted citation impact, top 9% 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.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · 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.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 22 citations in OpenAlex.

  1. Effects of SGLT2 inhibition on insulin use in CKD and type 2 diabetes: insights from the CREDENCE trial.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025 · on this map
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  12. An Overview of the Cardiorenal Protective Mechanisms of SGLT2 Inhibitors.International journal of molecular sciences · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 9 institutions in 5 countries.

Muthiah VaduganathanDivision of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.ORCID 0000-0003-0885-1953
Silvio E InzucchiSection of Endocrinology, Yale School of Medicine, Yale University, New Haven, Connecticut, USA.ORCID 0000-0003-1254-6636
Naveed SattarUniversity of Glasgow, Glasgow, UK.ORCID 0000-0002-1604-2593
David H FitchettDivision of Cardiology, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.ORCID 0000-0002-1312-5983
Anne Pernille OfstadMedical Department, Boehringer Ingelheim KS, Asker, Norway.
Martina BrueckmannBoehringer Ingelheim International GmbH, Ingelheim, Germany.
Jyothis T GeorgeBoehringer Ingelheim International GmbH, Ingelheim, Germany.
Subodh VermaDivision of Cardiac Surgery, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
Michaela MattheusBoehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany.
Christoph WannerDepartment of Internal Medicine I, Nephrology, University Hospital Würzburg, Würzburg, Germany.
Bernard ZinmanLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.ORCID 0000-0002-0041-1876
Javed ButlerDepartment of Medicine, University of Mississippi, Jackson, Mississippi, USA.
Boehringer Ingelheim (Germany) · DESt. Michael's Hospital · CAAIDS Clinical Trials Group · USBoehringer Ingelheim (Norway) · NOBrigham and Women's Hospital · USMount Sinai Hospital · CAUniversitätsklinikum Würzburg · DEUniversity of Glasgow · GBYale University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimTo evaluate the effects of empagliflozin versus placebo on subsequent insulin initiation or dosing changes in a large cardiovascular outcomes trial. MATERIALS AND

methodsIn EMPA-REG OUTCOME, 7020 patients with type 2 diabetes and cardiovascular disease received empagliflozin 10 mg, 25 mg, or placebo. Median follow-up was 3.1 years. After 12 weeks of treatment, changes in background antihyperglycaemic therapy were permitted. Among insulin-naïve patients, we assessed the effects of pooled empagliflozin arms versus placebo on time to initiation of insulin. Among insulin-treated patients, we assessed effects on time to an increase or decrease in insulin dose of more than 20%.

resultsIn 3633 (52%) participants not treated with insulin at baseline, empagliflozin reduced new use of insulin versus placebo by 60% (7.1% vs. 16.4%; adjusted HR 0.40 [95% CI 0.32-0.49]; P < .0001). In 3387 (48%) patients using insulin at baseline, empagliflozin reduced the need for a greater than 20% insulin dose increase by 58% (14.4% vs. 29.3%; adjusted HR 0.42 [95% CI 0.36-0.49]; P < .0001) and increased the proportion achieving sustained greater than 20% insulin dose reductions without subsequent increases in HbA1c compared with placebo (9.2% vs. 4.9%; adjusted HR 1.87 [95% CI: 1.39-2.51]; P < .0001). Sensitivity analyses confirmed consistent findings when insulin dose changes of more than 10% or more than 30% were considered.

conclusionsIn patients with type 2 diabetes and cardiovascular disease, empagliflozin markedly and durably delays insulin initiation and substantial increases in insulin dose, while facilitating sustained reductions in insulin requirements over time.

Indexed as

Cardiovascular DiseasesDiabetes Mellitus, Type 2Sodium-Glucose Transporter 2 InhibitorsBenzhydryl CompoundsGlucosidesHumansHypoglycemic AgentsInsulinTreatment OutcomeBenzhydryl CompoundsempagliflozinGlucosidesHypoglycemic AgentsInsulinSodium-Glucose Transporter 2 Inhibitorsdiabetesinsulinsodium-glucose co-transporter-2 inhibitors

Identifiers

PMID34463409
PMCPMC9291462
OpenAlexW3197785709

What Socratic holds

Textmetadata
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.