Evidence map›Paper›PMID 31005993›Full record

ArticleNephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association2020

Prediction of the effect of dapagliflozin on kidney and heart failure outcomes based on short-term changes in multiple risk markers.

Nienke M A Idzerda, Bergur V Stefansson, Michelle J Pena, David C Sjostrom, David C Wheeler, Hiddo J L Heerspink

Open access · bronzeAbstract read
In one paragraph

Article in Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.4field-weighted citation impact, top 18% 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

7 citing papers in PubMed, 11 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Review
  4. Article
  5. Precision medicine approaches for diabetic kidney disease: opportunities and challenges.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2021
    Review
  6. Article
  7. Article
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

6 authors at 3 institutions in 3 countries.

Nienke M A IdzerdaDepartment of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Bergur V StefanssonAstraZeneca, Gothenburg, Sweden.
Michelle J PenaDepartment of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
David C SjostromAstraZeneca, Gothenburg, Sweden.
David C WheelerDepartment of Renal Medicine, University College London, London, UK.
Hiddo J L HeerspinkDepartment of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
University Medical Center Groningen · NLAstraZeneca (Sweden) · SEUniversity College London · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundBesides improving glucose control, sodium-glucose co-transporter 2 inhibition with dapagliflozin reduces blood pressure, body weight and urinary albumin:creatinine ratio (UACR) in patients with type 2 diabetes (T2DM). The parameter response efficacy (PRE) score was developed to predict how short-term drug effects on cardiovascular risk markers translate into long-term changes in clinical outcomes. We applied the PRE score to clinical trials of dapagliflozin to model the effect of the drug on kidney and heart failure (HF) outcomes in patients with T2DM and impaired kidney function.

methodsThe relationships between multiple risk markers and long-term outcome were determined in a background population of patients with T2DM with a multivariable Cox model. These relationships were then applied to short-term changes in risk markers observed in a pooled database of dapagliflozin trials (n = 7) that recruited patients with albuminuria to predict the drug-induced changes to kidney and HF outcomes.

resultsA total of 132 and 350 patients had UACR >200 mg/g and >30 mg/g at baseline, respectively, and were selected for analysis. The PRE score predicted a risk change for kidney events of -40.8% [95% confidence interval (CI) -51.7 to -29.4) and -40.4% (95% CI -48.4 to -31.1) with dapagliflozin 10 mg compared with placebo for the UACR >200 mg/g and >30 mg/g subgroups. The predicted change in risk for HF events was -27.3% (95% CI -47.7 to -5.1) and -21.2% (95% CI -35.0 to -7.8), respectively. Simulation analyses showed that even with a smaller albuminuria-lowering effect of dapagliflozin (10% instead of the observed 35% in both groups), the estimated kidney risk reduction was still 26.5 and 26.8%, respectively.

conclusionsThe PRE score predicted clinically meaningful reductions in kidney and HF events associated with dapagliflozin therapy in patients with diabetic kidney disease. These results support a large long-term outcome trial in this population to confirm the benefits of the drug on these endpoints.

Indexed as

AgedAlbuminuriaBenzhydryl CompoundsBiomarkersClinical Trials, Phase III as TopicDiabetes Mellitus, Type 2Diabetic NephropathiesFemaleGlucosidesHeart FailureHumansMaleMiddle AgedSodium-Glucose Transporter 2 InhibitorsTreatment OutcomeBenzhydryl CompoundsBiomarkersdapagliflozinGlucosidesSodium-Glucose Transporter 2 Inhibitorsclinical trialdapagliflozindiabetic kidney diseaseheart failurerisk markers

Identifiers

PMID31005993
PMCPMC7473803
OpenAlexW2936772405

What OpenQuestion holds

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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.