Evidence map›Paper›PMID 27299675›Full record

Trial reportThe New England journal of medicine2016

Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes.

Christoph Wanner, Silvio E Inzucchi, John M Lachin, David Fitchett, Maximilian von Eynatten, Michaela Mattheus, Odd Erik Johansen, Hans J Woerle, Uli C Broedl, Bernard Zinman and 1 more

11 registry-linked trialsAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in The New England journal of medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 11 registered trials, which are not on this map. Cited by 1,558 papers, 11 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1,558citing papers in PubMed, 11 pooled it
–field-weighted citation impact
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.

NCT03132181 phase2completedstarted 2017, after this paper: background citation

Empagliflozin as a Modulator of Systemic Vascular Resistance and Cardiac Output in Patients With Type 2 Diabetes

Ran2017Enrolled40Registered outcomes14Posted comparisons0ConditionsDiabetes Mellitus Type 2 (T2DM)Armsempagliflozin, Placebo
PMID 24939043PMID 24444522PMID 23735727PMID 24026259PMID 24475922PMID 26343814PMID 26981940other papers from this trial
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NCT03173963 phase3withdrawnstarted 2017, after this paper: background citation

Empagliflozin in Early Diabetic Kidney Disease

Ran2017Enrolled0Registered outcomes4Posted comparisons0ConditionsDiabetes Mellitus Type 2, Diabetic Kidney DiseaseArmsempagliflozin, Placebo
PMID 10361863PMID 26378978other papers from this trial
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NCT03200860 phase2completedstarted 2017, after this paper: background citation

Randomized, Double Blind, Placebo Controlled, Multicenter Pilot Study on the Effects of Empagliflozin on Clinical Outcomes in Patients With Acute Decompensated Heart Failure (EMPA-RESPONSE-AHF)

Ran2017Enrolled80Registered outcomes8Posted comparisons6ConditionsHeart Failure Acute, Heart Failure，Congestive, Heart Failure; With DecompensationArmsempagliflozin 10 mg, Placebo Oral Tablet
PMID 26378978other papers from this trial
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NCT03887416 phase4unknown statusstarted 2019, after this paper: background citation

Effect of Dapagliflozin on Nighttime Blood Pressure in Type 2 Diabetes

Ran2019Enrolled225Registered outcomes4Posted comparisons0ConditionsType2 DiabetesArmsDapagliflozin 10 MG Oral Tablet [Farxiga], Placebo Oral Tablet
PMID 22080225PMID 12226150PMID 12493255PMID 18456100PMID 1969567PMID 20216407PMID 22027655PMID 23245609PMID 23771844PMID 23989362PMID 24886823PMID 25033166other papers from this trial
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NCT03933956 phase3terminatedstarted 2020, after this paper: background citation

Metabolic Effects of the SGLT-2 Inhibitor Empagliflozin in Patients With Diabetic Nephropathy (MEDiaN)

Ran2020Enrolled2Registered outcomes3Posted comparisons0ConditionsDiabetic NephropathiesArmsempagliflozin 10 mg
PMID 24463454PMID 27289124PMID 28395981PMID 24026259PMID 23949796PMID 29142974other papers from this trial
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NCT04203927 early_phase1unknown statusstarted 2020, after this paper: background citation

Effects of Empagliflozin on Cardiac Microvasculature and Insulin Sensitivity in Subjects With Type 2 Diabetes

Ran2020Enrolled50Registered outcomes4Posted comparisons0ConditionsInsulin Sensitivity, Type2 DiabetesArmsempagliflozin 25 mg
PMID 29166232PMID 15998667PMID 28304392PMID 29203583PMID 16308832PMID 16386091PMID 19996061PMID 20380649PMID 20978231PMID 21047922PMID 21617098PMID 23459195other papers from this trial
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NCT05037695 phase4unknown statusstarted 2021, after this paper: background citation

SGLT-2 Inhibitors in Prevention of Post-procedural Renal and Cardiovascular Complications aFter PCI Among Patients With Diabetes Mellitus and Coronary Artery Disease: a Prospective, Randomized, Pilot Study (SAFE-PCI)

Ran2021Enrolled40Registered outcomes17Posted comparisons0ConditionsAcute Kidney Injury, Coronary Artery Disease, Diabetes Mellitus, Type 2Armsempagliflozin 25 mg
PMID 30990260PMID 28792984PMID 11565518PMID 16612394PMID 17184637PMID 17699010PMID 18287807PMID 19850388PMID 20686453PMID 23895807PMID 24135581PMID 24226524other papers from this trial
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NCT01131676 phase3completednot on this map

A Phase III, Multicentre, International, Randomised, Parallel Group, Double Blind Cardiovascular Safety Study of BI 10773 (10 mg and 25 mg Administered Orally Once Daily) Compared to Usual Care in Type 2 Diabetes Mellitus Patients With Increased Cardiovascular Risk

TypeinterventionalSponsorBoehringer IngelheimRan2010 to 2015Enrolled7,064ConditionsDiabetes Mellitus, Type 2ArmsBI 10773 low dose, Placebo BI 10773 high dose, BI 10773 high dose, Placebo BI 10773 low dose
NCT03878706 recruitingnot on this mapstarted 2017, after this paper: background citation

The Effect of GLP-1 Agonist, SGLT2 Inhibitor and Their Combination on Endothelial Function, Arterial Stiffness and Left Ventricular Deformation in Patients With Type 2 Diabetes With High Cardiovascular Risk

Typeobservational_patient_registrySponsorUniversity of AthensRan2017 to 2027Enrolled240ConditionsDiabetes Mellitus, Type 2
NCT05349955 narecruitingnot on this mapstarted 2022, after this paper: background citation

Effects and Safety of GUideline Algorithm Based Intervention on CaRdiovascular and Renal Outcomes in Elderly Diabetic Patients With High Cardiovascular Risk in the Community- A Cluster Randomized Controlled Trial (GUARD-Community Study)

TypeinterventionalSponsorShanghai Zhongshan HospitalRan2022 to 2026Enrolled5,600ConditionsType 2 Diabetes, Cardiovascular Complication, Diabetic Kidney DiseaseArmsIntensive guideline algorithm implementation, Conventional guideline algorithm implementation
NCT05417880 phase3unknown statusnot on this mapstarted 2022, after this paper: background citation

Vitamin D, K2 Plus Empagliflozin Combination in Type Two Diabetes Mellitus

TypeinterventionalSponsorScotmann PharmaceuticalsRan2022 to 2023Enrolled340ConditionsDiabetes MellitusArmsOral Hypoglycemic Agents,Oral, Voreta, Voreta plus SunnyD PRO
3 · Its place in the literature

Who cites it

1,558 citing papers in PubMed, 11 syntheses or guidelines pooled it.

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1,498 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Christoph WannerFrom the Department of Medicine, Division of Nephrology, Würzburg University Clinic, Würzburg (C.W.), and Boehringer Ingelheim Pharma, Ingelheim (M.E., M.M., H.J.W., U.C.B.) - both in Germany; the Section of Endocrinology, Yale University School of Medicine, New Haven, CT (S.E.I.); the Biostatistics Center, George Washington University, Rockville, MD (J.M.L.); the Divisions of Cardiology (D.F.) and Endocrinology (B.Z.), University of Toronto, and the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital (B.Z.) - both in Toronto; and Boehringer Ingelheim Norway, Asker, Norway (O.E.J.).
Silvio E InzucchiFrom the Department of Medicine, Division of Nephrology, Würzburg University Clinic, Würzburg (C.W.), and Boehringer Ingelheim Pharma, Ingelheim (M.E., M.M., H.J.W., U.C.B.) - both in Germany; the Section of Endocrinology, Yale University School of Medicine, New Haven, CT (S.E.I.); the Biostatistics Center, George Washington University, Rockville, MD (J.M.L.); the Divisions of Cardiology (D.F.) and Endocrinology (B.Z.), University of Toronto, and the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital (B.Z.) - both in Toronto; and Boehringer Ingelheim Norway, Asker, Norway (O.E.J.).
John M LachinFrom the Department of Medicine, Division of Nephrology, Würzburg University Clinic, Würzburg (C.W.), and Boehringer Ingelheim Pharma, Ingelheim (M.E., M.M., H.J.W., U.C.B.) - both in Germany; the Section of Endocrinology, Yale University School of Medicine, New Haven, CT (S.E.I.); the Biostatistics Center, George Washington University, Rockville, MD (J.M.L.); the Divisions of Cardiology (D.F.) and Endocrinology (B.Z.), University of Toronto, and the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital (B.Z.) - both in Toronto; and Boehringer Ingelheim Norway, Asker, Norway (O.E.J.).
David FitchettFrom the Department of Medicine, Division of Nephrology, Würzburg University Clinic, Würzburg (C.W.), and Boehringer Ingelheim Pharma, Ingelheim (M.E., M.M., H.J.W., U.C.B.) - both in Germany; the Section of Endocrinology, Yale University School of Medicine, New Haven, CT (S.E.I.); the Biostatistics Center, George Washington University, Rockville, MD (J.M.L.); the Divisions of Cardiology (D.F.) and Endocrinology (B.Z.), University of Toronto, and the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital (B.Z.) - both in Toronto; and Boehringer Ingelheim Norway, Asker, Norway (O.E.J.).
Maximilian von EynattenFrom the Department of Medicine, Division of Nephrology, Würzburg University Clinic, Würzburg (C.W.), and Boehringer Ingelheim Pharma, Ingelheim (M.E., M.M., H.J.W., U.C.B.) - both in Germany; the Section of Endocrinology, Yale University School of Medicine, New Haven, CT (S.E.I.); the Biostatistics Center, George Washington University, Rockville, MD (J.M.L.); the Divisions of Cardiology (D.F.) and Endocrinology (B.Z.), University of Toronto, and the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital (B.Z.) - both in Toronto; and Boehringer Ingelheim Norway, Asker, Norway (O.E.J.).
Michaela MattheusFrom the Department of Medicine, Division of Nephrology, Würzburg University Clinic, Würzburg (C.W.), and Boehringer Ingelheim Pharma, Ingelheim (M.E., M.M., H.J.W., U.C.B.) - both in Germany; the Section of Endocrinology, Yale University School of Medicine, New Haven, CT (S.E.I.); the Biostatistics Center, George Washington University, Rockville, MD (J.M.L.); the Divisions of Cardiology (D.F.) and Endocrinology (B.Z.), University of Toronto, and the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital (B.Z.) - both in Toronto; and Boehringer Ingelheim Norway, Asker, Norway (O.E.J.).
Odd Erik JohansenFrom the Department of Medicine, Division of Nephrology, Würzburg University Clinic, Würzburg (C.W.), and Boehringer Ingelheim Pharma, Ingelheim (M.E., M.M., H.J.W., U.C.B.) - both in Germany; the Section of Endocrinology, Yale University School of Medicine, New Haven, CT (S.E.I.); the Biostatistics Center, George Washington University, Rockville, MD (J.M.L.); the Divisions of Cardiology (D.F.) and Endocrinology (B.Z.), University of Toronto, and the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital (B.Z.) - both in Toronto; and Boehringer Ingelheim Norway, Asker, Norway (O.E.J.).
Hans J WoerleFrom the Department of Medicine, Division of Nephrology, Würzburg University Clinic, Würzburg (C.W.), and Boehringer Ingelheim Pharma, Ingelheim (M.E., M.M., H.J.W., U.C.B.) - both in Germany; the Section of Endocrinology, Yale University School of Medicine, New Haven, CT (S.E.I.); the Biostatistics Center, George Washington University, Rockville, MD (J.M.L.); the Divisions of Cardiology (D.F.) and Endocrinology (B.Z.), University of Toronto, and the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital (B.Z.) - both in Toronto; and Boehringer Ingelheim Norway, Asker, Norway (O.E.J.).
Uli C BroedlFrom the Department of Medicine, Division of Nephrology, Würzburg University Clinic, Würzburg (C.W.), and Boehringer Ingelheim Pharma, Ingelheim (M.E., M.M., H.J.W., U.C.B.) - both in Germany; the Section of Endocrinology, Yale University School of Medicine, New Haven, CT (S.E.I.); the Biostatistics Center, George Washington University, Rockville, MD (J.M.L.); the Divisions of Cardiology (D.F.) and Endocrinology (B.Z.), University of Toronto, and the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital (B.Z.) - both in Toronto; and Boehringer Ingelheim Norway, Asker, Norway (O.E.J.).
Bernard ZinmanFrom the Department of Medicine, Division of Nephrology, Würzburg University Clinic, Würzburg (C.W.), and Boehringer Ingelheim Pharma, Ingelheim (M.E., M.M., H.J.W., U.C.B.) - both in Germany; the Section of Endocrinology, Yale University School of Medicine, New Haven, CT (S.E.I.); the Biostatistics Center, George Washington University, Rockville, MD (J.M.L.); the Divisions of Cardiology (D.F.) and Endocrinology (B.Z.), University of Toronto, and the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital (B.Z.) - both in Toronto; and Boehringer Ingelheim Norway, Asker, Norway (O.E.J.).
EMPA-REG OUTCOME Investigators

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDiabetes confers an increased risk of adverse cardiovascular and renal events. In the EMPA-REG OUTCOME trial, empagliflozin, a sodium-glucose cotransporter 2 inhibitor, reduced the risk of major adverse cardiovascular events in patients with type 2 diabetes at high risk for cardiovascular events. We wanted to determine the long-term renal effects of empagliflozin, an analysis that was a prespecified component of the secondary microvascular outcome of that trial.

methodsWe randomly assigned patients with type 2 diabetes and an estimated glomerular filtration rate of at least 30 ml per minute per 1.73 m(2) of body-surface area to receive either empagliflozin (at a dose of 10 mg or 25 mg) or placebo once daily. Prespecified renal outcomes included incident or worsening nephropathy (progression to macroalbuminuria, doubling of the serum creatinine level, initiation of renal-replacement therapy, or death from renal disease) and incident albuminuria.

resultsIncident or worsening nephropathy occurred in 525 of 4124 patients (12.7%) in the empagliflozin group and in 388 of 2061 (18.8%) in the placebo group (hazard ratio in the empagliflozin group, 0.61; 95% confidence interval, 0.53 to 0.70; P<0.001). Doubling of the serum creatinine level occurred in 70 of 4645 patients (1.5%) in the empagliflozin group and in 60 of 2323 (2.6%) in the placebo group, a significant relative risk reduction of 44%. Renal-replacement therapy was initiated in 13 of 4687 patients (0.3%) in the empagliflozin group and in 14 of 2333 patients (0.6%) in the placebo group, representing a 55% lower relative risk in the empagliflozin group. There was no significant between-group difference in the rate of incident albuminuria. The adverse-event profile of empagliflozin in patients with impaired kidney function at baseline was similar to that reported in the overall trial population.

conclusionsIn patients with type 2 diabetes at high cardiovascular risk, empagliflozin was associated with slower progression of kidney disease and lower rates of clinically relevant renal events than was placebo when added to standard care. (Funded by the Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance; EMPA-REG OUTCOME ClinicalTrials.gov number, NCT01131676.).

Indexed as

AgedAlbuminuriaBenzhydryl CompoundsCardiovascular DiseasesDiabetes Mellitus, Type 2Diabetic NephropathiesDisease ProgressionFemaleGlomerular Filtration RateGlucosidesHumansHypoglycemic AgentsIntention to Treat AnalysisKaplan-Meier EstimateKidneyMaleBenzhydryl CompoundsempagliflozinGlucosidesHypoglycemic Agents

Identifiers

PMID27299675

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.