Evidence map›Paper›PMID 34129237›Full record

SynthesisClinical cardiology2021

Kidney outcomes using a sustained ≥40% decline in eGFR: A meta-analysis of SGLT2 inhibitor trials.

David Z I Cherney, Samuel Dagogo-Jack, Darren K McGuire, Francesco Cosentino, Richard Pratley, Weichung J Shih, Robert Frederich, Mario Maldonado, Jie Liu, Shuai Wang and 2 more

5 registry-linked trialsOpen access · goldAbstract readMeta-Analysis
In one paragraph

Synthesis in Clinical cardiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT01032629. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
3.4field-weighted citation impact, top 7% 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.

NCT01032629 phase3completed

A Randomized, Multicenter, Double-Blind, Parallel, Placebo-Controlled Study of the Effects of JNJ-28431754 on Cardiovascular Outcomes in Adult Subjects With Type 2 Diabetes Mellitus

Ran2009Enrolled4,330Registered outcomes13Posted comparisons33ConditionsCardiovascular Diseases, Diabetes Mellitus, Type 2, Risk FactorsArmsCanagliflozin (JNJ-28431754) 100 mg, Canagliflozin (JNJ-28431754) 300 mg, Placebo
Open the trial in the graph
NCT01730534 phase3completed

Dapagliflozin Effect on Cardiovascular Events A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Effect of Dapagliflozin 10 mg Once Daily on the Incidence of Cardiovascular Death, Myocardial Infarction or Ischemic Stroke in Patients With Type 2 Diabetes

Ran2013Enrolled17,190Registered outcomes4Posted comparisons4ConditionsDiabetes Mellitus, Non-Insulin-Dependent, High Risk for Cardiovascular EventArmsDapagliflozin 10 mg, Placebo tablet
Open the trial in the graph
NCT01989754 phase4completed

A Randomized, Multicenter, Double-Blind, Parallel, Placebo-Controlled Study of the Effects of Canagliflozin on Renal Endpoints in Adult Subjects With Type 2 Diabetes Mellitus

Ran2014Enrolled5,813Registered outcomes3Posted comparisons3ConditionsAlbuminuria, Diabetes Mellitus, Type 2ArmsCanagliflozin, 100 mg, Canagliflozin, 300 mg, Placebo
Open the trial in the graph
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
NCT01986881 phase3completednot on this map

Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Assess Cardiovascular Outcomes Following Treatment With Ertugliflozin (MK-8835/PF-04971729) in Subjects With Type 2 Diabetes Mellitus and Established Vascular Disease, The VERTIS CV Study

TypeinterventionalSponsorMerck Sharp & Dohme LLCRan2013 to 2019Enrolled8,246ConditionsType 2 Diabetes MellitusArmsErtugliflozin, Placebo, Glycemic Rescue
3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Article
  5. Review
  6. Article
  7. Article
  8. SGLT2 Inhibitors in Kidney Diseases-A Narrative Review.International journal of molecular sciences · 2024
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Review
  17. The Place and Value of Sodium-Glucose Cotransporter 2 Inhibitors in the Evolving Treatment Paradigm for Type 2 Diabetes Mellitus: A Narrative Review.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2022 · on this map
    Review
  18. Review
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 10 institutions in 4 countries.

David Z I CherneyDivision of Nephrology, University of Toronto, Toronto, Ontario, Canada.ORCID https://orcid.org/0000-0003-4164-0429
Samuel Dagogo-JackDivision of Endocrinology, Diabetes and Metabolism, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
Darren K McGuireDivision of Cardiology, University of Texas Southwestern Medical Center, and Parkland Health and Hospital System, Dallas, Texas, USA.
Francesco CosentinoUnit of Cardiology, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden.
Richard PratleyAdventHealth Translational Research Institute, Orlando, Florida, USA.
Weichung J ShihDepartment of Biostatistics and Epidemiology, Rutgers School of Public Health and Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA.
Robert FrederichClinical Development and Operations, Research and Development, Pfizer Inc., Collegeville, Pennsylvania, USA.
Mario MaldonadoDiabetes and Endocrinology, MSD Limited, London, UK.
Jie LiuGlobal Product Development Statistics, Merck & Co., Inc., Kenilworth, New Jersey, USA.
Shuai WangPfizer Inc., Groton, Connecticut, USA.
Christopher P CannonCardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.ORCID https://orcid.org/0000-0003-4596-2791
VERTIS CV Investigators
Pfizer (United States) · USBrigham and Women's Hospital · USDiabetes UK · GBKarolinska University Hospital · SEMerck & Co., Inc., Rahway, NJ, USA (United States) · USParkland Health & Hospital System · USRutgers, The State University of New Jersey · USTranslational Research Institute for Metabolism and Diabetes · USUniversity of Tennessee Health Science Center · USUniversity of Toronto · CA

Funding

Merck Sharp and DohmePfizer
6 · The paper itself

Abstract

backgroundA recent meta-analysis of sodium-glucose cotransporter 2 (SGLT2) inhibitor outcome trials reported that SGLT2 inhibitors were associated with reduction in the risk of adverse composite kidney outcomes, with moderate heterogeneity across the trials; however, the endpoints were defined differently across the trials. HYPOTHESIS: The apparent heterogeneity of the meta-analysis of kidney composite outcomes of SGLT2 inhibitor trials will be substantially reduced by using a consistent assessment of sustained ≥40% decline in eGFR/chronic kidney dialysis/transplantation/renal death across trials.

methodsWe performed a meta-analysis of kidney composite outcomes from the four SGLT2 cardiovascular outcome trial programs conducted in general type 2 diabetes mellitus populations, which included, as a surrogate of progression to kidney failure, a sustained ≥40% decline in eGFR along with kidney replacement therapy and kidney death. The trials assessed were VERTIS CV (NCT01986881), CANVAS Program (NCT01032629 and NCT01989754), DECLARE-TIMI 58 (NCT01730534), and EMPA-REG OUTCOME (NCT01131676).

resultsData from the trials comprised 42 516 individual participants; overall, 998 composite kidney events occurred. SGLT2 inhibition was associated with a significant reduction in the kidney composite endpoint (HR 0.58 [95% CI 0.51-0.65]) and with a highly consistent effect across the trials (Q statistic p = .64; I

conclusionsOur meta-analysis highlights the value of using similarly defined endpoints across trials and supports the finding of consistent protection against kidney disease progression with SGLT2 inhibitors as a class in patients with type 2 diabetes mellitus who either have established atherosclerotic cardiovascular disease or are at high cardiovascular risk with multiple cardiovascular risk factors.

Indexed as

Cardiovascular DiseasesDiabetes Mellitus, Type 2Sodium-Glucose Transporter 2 InhibitorsGlomerular Filtration RateHumansKidneySodium-Glucose Transporter 2 Inhibitorskidney diseasekidney failuremeta-analysisrandomized clinical trialsSGLT2 inhibitortype 2 diabetes mellitus

Identifiers

PMID34129237
PMCPMC8364727
OpenAlexW3172415017

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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.