Evidence map›Paper›PMID 30424892›Full record

SynthesisLancet (London, England)2019

SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials.

Thomas A Zelniker, Stephen D Wiviott, Itamar Raz, Kyungah Im, Erica L Goodrich, Marc P Bonaca, Ofri Mosenzon, Eri T Kato, Avivit Cahn, Remo H M Furtado and 5 more

Erratum issued 4 registry-linked trialsAbstract readMeta-AnalysisSystematic Review
PubMed Publisher
In one paragraph

Synthesis in Lancet (London, England), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 4 registered trials, which are not on this map. Cited by 1,245 papers, 14 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1,245citing papers in PubMed, 14 pooled it
232.9field-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.

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.

NCT06286878 phase2 / phase3recruitingstarted 2021, after this paper: background citation

Pleiotropic Effects of Dapagliflozin in Patients With Acute Coronary Syndromes

Ran2021Enrolled80Registered outcomes4Posted comparisons0ConditionsAcute Coronary Syndrome, Diabetes, Myocardial Infarction, Ventricular DysfunctionArmsdapagliflozin, Placebo
PMID 14502100PMID 28605608PMID 21205121PMID 26026848PMID 27295427PMID 28522450PMID 11602624PMID 11179406PMID 11595605PMID 16046311PMID 17852797PMID 18358749other papers from this trial
Open the trial in the graph
NCT07025629 phase3recruitingstarted 2025, after this paper: background citation

Dapagliflozin for Cardio-renal Protection After ICU Discharge: A Prospective, Randomized, Double Blinded, Multicenter Study: "DAPA-ICU Trial"

Ran2025Enrolled600Registered outcomes19Posted comparisons0ConditionsHeart Failure and Chronic Kidney Disease Post-ICUArmsDapagliflozin 10 MG Oral Tablet [Farxiga], One tablet of placebo of dapagliflozin 10 mg
PMID 32877652PMID 32492305PMID 31009585PMID 30045823PMID 32516543PMID 29347987PMID 27391020other papers from this trial
Open the trial in the graph
NCT04791826 nacompletednot on this mapstarted 2021, after this paper: background citation

Evaluation of an EMR-Based Clinical Decision Support Tool for the Implementation of Guideline-Directed Therapies for Prevention of Heart Failure Among High-Risk Patients With Type 2 Diabetes

TypeinterventionalSponsorUniversity of Texas Southwestern Medical CenterRan2021 to 2024Enrolled1,524ConditionsHeart Failure, Diabetes Mellitus, Type 2ArmsOn-screen electronic alert
NCT06444711 naactive not recruitingnot on this mapstarted 2025, after this paper: background citation

A Randomised Clinical Trial for OPTIMISation of Cardio-renal-metabolic-pulmonary Disease Guideline Adherence in High Risk Community Dwelling Individuals and Evaluation of Outcomes

TypeinterventionalSponsorUniversity of LeedsRan2025 to 2045Enrolled138ConditionsCardiovascular Diseases, Renal Disease, Metabolic Disease, Pulmonary DiseaseArmsNICE guidance
3 · Its place in the literature

Who cites it

1,245 citing papers in PubMed, 14 syntheses or guidelines pooled it, 2,745 citations in OpenAlex.

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1,185 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 8 institutions in 5 countries.

Thomas A ZelnikerTIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA.
Stephen D WiviottTIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA.
Itamar RazThe Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Hebrew University of Jerusalem, The Faculty of Medicine, Jerusalem, Israel.
Kyungah ImTIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA.
Erica L GoodrichTIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA.
Marc P BonacaTIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA.
Ofri MosenzonThe Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Hebrew University of Jerusalem, The Faculty of Medicine, Jerusalem, Israel.
Eri T KatoDepartment of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Avivit CahnThe Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Hebrew University of Jerusalem, The Faculty of Medicine, Jerusalem, Israel.
Remo H M FurtadoTIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA.
Deepak L BhattTIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA.
Lawrence A LeiterLi Ka Shing Knowledge Institute, St Michael's Hospital, University of Toronto, Toronto, ON, Canada.
Darren K McGuireDivision of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
John P H WildingInstitute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.
Marc S SabatineTIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA. Electronic address: msabatine@bwh.harvard.edu.
Thrombolysis in Myocardial Infarction Study Group · USBrigham and Women's Hospital · USHebrew University of Jerusalem · ILHadassah Medical Center · ILKyoto University · JPSt. Michael's Hospital · CAThe University of Texas Southwestern Medical Center · USUniversity of Liverpool · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe magnitude of effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on specific cardiovascular and renal outcomes and whether heterogeneity is based on key baseline characteristics remains undefined.

methodsWe did a systematic review and meta-analysis of randomised, placebo-controlled, cardiovascular outcome trials of SGLT2i in patients with type 2 diabetes. We searched PubMed and Embase for trials published up to Sept 24, 2018. Data search and extraction were completed with a standardised data form and any discrepancies were resolved by consensus. Efficacy outcomes included major adverse cardiovascular events (myocardial infarction, stroke, or cardiovascular death), the composite of cardiovascular death or hospitalisation for heart failure, and progression of renal disease. Hazard ratios (HRs) with 95% CIs were pooled across trials, and efficacy outcomes were stratified by baseline presence of atherosclerotic cardiovascular disease, heart failure, and degree of renal function.

findingsWe included data from three identified trials and 34 322 patients (60·2% with established atherosclerotic cardiovascular disease), with 3342 major adverse cardiovascular events, 2028 cardiovascular deaths or hospitalisation sfor heart failure events, and 766 renal composite outcomes. SGLT2i reduced major adverse cardiovascular events by 11% (HR 0·89 [95% CI 0·83-0·96], p=0·0014), with benefit only seen in patients with atherosclerotic cardiovascular disease (0·86 [0·80-0·93]) and not in those without (1·00 [0·87-1·16], p for interaction=0·0501). SGLT2i reduced the risk of cardiovascular death or hospitalisation for heart failure by 23% (0·77 [0·71-0·84], p<0·0001), with a similar benefit in patients with and without atherosclerotic cardiovascular disease and with and without a history of heart failure. SGLT2i reduced the risk of progression of renal disease by 45% (0·55 [0·48-0·64], p<0·0001), with a similar benefit in those with and without atherosclerotic cardiovascular disease. The magnitude of benefit of SGLT2i varied with baseline renal function, with greater reductions in hospitalisations for heart failure (p for interaction=0·0073) and lesser reductions in progression of renal disease (p for interaction=0·0258) in patients with more severe kidney disease at baseline.

interpretationSGLT2i have moderate benefits on atherosclerotic major adverse cardiovascular events that seem confined to patients with established atherosclerotic cardiovascular disease. However, they have robust benefits on reducing hospitalisation for heart failure and progression of renal disease regardless of existing atherosclerotic cardiovascular disease or a history of heart failure.

fundingNone.

Indexed as

Cardiovascular DiseasesDiabetes Mellitus, Type 2Diabetic NephropathiesHumansPrimary PreventionSecondary PreventionSodium-Glucose Transporter 2 InhibitorsSodium-Glucose Transporter 2 Inhibitors

Identifiers

PMID30424892
OpenAlexW2899764361

What Socratic holds

Textmetadata
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.