Evidence map›Paper›PMID 31791665›Full record

Trial reportKidney international2020

The renal hemodynamic effects of the SGLT2 inhibitor dapagliflozin are caused by post-glomerular vasodilatation rather than pre-glomerular vasoconstriction in metformin-treated patients with type 2 diabetes in the randomized, double-blind RED trial.

Erik J M van Bommel, Marcel H A Muskiet, Michaël J B van Baar, Lennart Tonneijck, Mark M Smits, Anna L Emanuel, Andrea Bozovic, A H Jan Danser, Frank Geurts, Ewout J Hoorn and 7 more

Erratum issuedOpen access · greenAbstract readClinical Trial, Phase IVComparative StudyRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in Kidney international, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 188 papers, 12 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
188citing papers in PubMed, 12 pooled it
28.1field-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.

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

188 citing papers in PubMed, 12 syntheses or guidelines pooled it, 335 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Pooled it
  8. Pooled it
  9. Pooled it
  10. Pooled it
  11. Pooled it
  12. Pooled it
  13. Trial
  14. Trial
  15. Trial
  16. Trial
  17. Volenrelaxin (LY3540378) increases renal plasma flow: a randomized Phase 1 trial.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024
    Trial
  18. How do SGLT2 inhibitors protect the kidney? A mediation analysis of the EMPA-REG OUTCOME trial.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024
    Trial
  19. Trial
  20. Trial

128 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 7 institutions in 3 countries.

Erik J M van BommelDiabetes Center, Department of Internal Medicine, Amsterdam University Medical Centers, location VUMC, Amsterdam, The Netherlands. Electronic address: e.vanbommel@amsterdamumc.nl.
Marcel H A MuskietDiabetes Center, Department of Internal Medicine, Amsterdam University Medical Centers, location VUMC, Amsterdam, The Netherlands.
Michaël J B van BaarDiabetes Center, Department of Internal Medicine, Amsterdam University Medical Centers, location VUMC, Amsterdam, The Netherlands.
Lennart TonneijckDiabetes Center, Department of Internal Medicine, Amsterdam University Medical Centers, location VUMC, Amsterdam, The Netherlands.
Mark M SmitsDiabetes Center, Department of Internal Medicine, Amsterdam University Medical Centers, location VUMC, Amsterdam, The Netherlands.
Anna L EmanuelDiabetes Center, Department of Internal Medicine, Amsterdam University Medical Centers, location VUMC, Amsterdam, The Netherlands.
Andrea BozovicDepartment of Clinical Biochemistry, University Health Network, University of Toronto, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology, University Health Network, University of Toronto, Toronto, Ontario, Canada.
A H Jan DanserDivision of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Frank GeurtsDivision of Nephrology and Transplantation, Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Ewout J HoornDivision of Nephrology and Transplantation, Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Daan J TouwDepartment of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, Groningen, The Netherlands.
Emil L LarsenDepartment of Clinical Pharmacology, Bispebjerg-Frederiksberg Hospital, Copenhagen, Denmark.
Henrik E PoulsenDepartment of Clinical Pharmacology, Bispebjerg-Frederiksberg Hospital, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Mark H H KramerDiabetes Center, Department of Internal Medicine, Amsterdam University Medical Centers, location VUMC, Amsterdam, The Netherlands.
Max NieuwdorpDiabetes Center, Department of Internal Medicine, Amsterdam University Medical Centers, location VUMC, Amsterdam, The Netherlands.
Jaap A JolesDepartment of Nephrology and Hypertension, University Medical Center, Utrecht, The Netherlands.
Daniël H van RaalteDiabetes Center, Department of Internal Medicine, Amsterdam University Medical Centers, location VUMC, Amsterdam, The Netherlands.
Amsterdam University Medical Centers · NLErasmus MC · NLFrederiksberg Hospital · DKUniversity Health Network · CAUniversity Medical Center Groningen · NLUniversity Medical Center Utrecht · NLUniversity of Copenhagen · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve hard renal outcomes in type 2 diabetes. This is possibly explained by the fact that SGLT2i normalize the measured glomerular filtration rate (mGFR) by increasing renal vascular resistance, as was shown in young people with type 1 diabetes and glomerular hyperfiltration. Therefore, we compared the renal hemodynamic effects of dapagliflozin with gliclazide in type 2 diabetes. The mGFR and effective renal plasma flow were assessed using inulin and para-aminohippurate clearances in the fasted state, during clamped euglycemia (5 mmol/L) and during clamped hyperglycemia (15 mmol/L). Filtration fraction and renal vascular resistance were calculated. Additionally, factors known to modulate renal hemodynamics were measured. In 44 people with type 2 diabetes on metformin monotherapy (Hemoglobin A1c 7.4%, mGFR 113 mL/min), dapagliflozin versus gliclazide reduced mGFR by 5, 10, and 12 mL/min in the consecutive phases while both agents similarly improved Hemoglobin A1c (-0.48% vs -0.65%). Dapagliflozin also reduced filtration fraction without increasing renal vascular resistance, and increased urinary adenosine and prostaglandin concentrations. Gliclazide did not consistently alter renal hemodynamic parameters. Thus, beyond glucose control, SGLT2i reduce mGFR and filtration fraction in type 2 diabetes. The fact that renal vascular resistance was not increased by dapagliflozin suggests that this is due to post-glomerular vasodilation rather than pre-glomerular vasoconstriction.

Indexed as

AgedBenzhydryl CompoundsDiabetes Mellitus, Type 2Diabetic NephropathiesDouble-Blind MethodFemaleGliclazideGlomerular Filtration RateGlucosidesGlycated HemoglobinHumansKidneyMaleMetforminMiddle AgedSodium-Glucose Transporter 2 InhibitorsBenzhydryl CompoundsdapagliflozinGliclazideGlucosidesGlycated Hemoglobinhemoglobin A1c protein, humanMetforminSodium-Glucose Transporter 2 Inhibitorsdiabetic kidney diseaserenal hemodynamicsSGLT2 inhibitiontype 2 diabetes

Identifiers

PMID31791665
OpenAlexW2980268988

What OpenQuestion holds

Texttitle and abstract
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 OpenQuestion graph.