Evidence mapPaperPMID 33592103Full record

Trial reportThe Journal of clinical endocrinology and metabolism2021

Effect of Dapagliflozin on Urine Metabolome in Patients with Type 2 Diabetes.

Evdoxia Bletsa, Sebastien Filippas-Dekouan, Christina Kostara, Panagiotis Dafopoulos, Aikaterini Dimou, Eleni Pappa, Styliani Chasapi, Georgios Spyroulias, Anastasios Koutsovasilis, Eleni Bairaktari and 2 more

Open access · hybridFull text readClinical Trial
In one paragraph

Trial report in The Journal of clinical endocrinology and metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 1 pooled it
4.3field-weighted citation impact, top 5% 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

24 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.

  1. SGLT2 inhibitors and nephrolithiasis risk: a meta-analysis.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025
    Pooled it
  2. Trial
  3. Trial
  4. Trial
  5. Effect of Dapagliflozin on Urine Metabolome in Patients with Type 2 Diabetes.The Journal of clinical endocrinology and metabolism · 2021
    Trial
  6. Review
  7. Review
  8. Article
  9. Article
  10. Dietary Interventions withFoods (Basel, Switzerland) · 2025
    Article
  11. Article
  12. Article
  13. Metabolomics Insights into the Benefits of SGLT2 Inhibitors in Type 2 Diabetes.Clinical pharmacology : advances and applications · 2025
    Review
  14. Article
  15. Review
  16. Diuretic effect and renal function impact of dapagliflozin in hospitalized patients with HFrEF.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2024
    Article
  17. Article
  18. Review
  19. Review
  20. 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

12 authors at 3 institutions in 2 countries.

Evdoxia BletsaThird Internal Medicine Department, General Hospital of Nikaia, Athens, Greece.
Sebastien Filippas-DekouanDepartment of Internal Medicine, University of Ioannina, Ioannina, Greece.
Christina KostaraLaboratory of Clinical Chemistry, University of Ioannina, Ioannina, Greece.
Panagiotis DafopoulosLaboratory of Clinical Chemistry, University of Ioannina, Ioannina, Greece.
Aikaterini DimouLaboratory of Clinical Chemistry, University of Ioannina, Ioannina, Greece.
Eleni PappaDepartment of Internal Medicine, University of Ioannina, Ioannina, Greece.
Styliani ChasapiDepartment of Pharmacy, University of Patras, Rio, Greece.
Georgios SpyrouliasDepartment of Pharmacy, University of Patras, Rio, Greece.
Anastasios KoutsovasilisThird Internal Medicine Department, General Hospital of Nikaia, Athens, Greece.
Eleni BairaktariLaboratory of Clinical Chemistry, University of Ioannina, Ioannina, Greece.
Ele FerranniniCNR Institute of Clinical Physiology, Pisa, Italy.
Vasilis TsimihodimosDepartment of Internal Medicine, University of Ioannina, Ioannina, Greece.
University of Ioannina · GRUniversity of Patras · GRIstituto di Fisiologia Clinica · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

contextInhibitors of sodium-glucose cotransporters-2 have cardio- and renoprotective properties. However, the underlying mechanisms remain indeterminate.

objectiveTo evaluate the effect of dapagliflozin on renal metabolism assessed by urine metabolome analysis in patients with type 2 diabetes.

designProspective cohort study.

settingOutpatient diabetes clinic of a tertiary academic center. PATIENTS: Eighty patients with hemoglobin A1c > 7% on metformin monotherapy were prospectively enrolled.

interventionFifty patients were treated with dapagliflozin for 3 months. To exclude that the changes observed in urine metabolome were merely the result of the improvement in glycemia, 30 patients treated with insulin degludec were used for comparison.

main outcome measureChanges in urine metabolic profile before and after the administration of dapagliflozin and insulin degludec were assessed by proton-nuclear magnetic resonance spectroscopy.

resultsIn multivariate analysis urine metabolome was significantly altered by dapagliflozin (R2X = 0.819, R2Y = 0.627, Q2Y = 0.362, and coefficient of variation analysis of variance, P < 0.001) but not insulin. After dapagliflozin, the urine concentrations of ketone bodies, lactate, branched chain amino acids (P < 0.001), betaine, myo-inositol (P < 0001), and N-methylhydantoin (P < 0.005) were significantly increased. Additionally, the urine levels of alanine, creatine, sarcosine, and citrate were also increased (P < 0001, P <0.0001, and P <0.0005, respectively) whereas anserine decreased (P < 0005).

conclusionsDapagliflozin significantly affects urine metabolome in patients with type 2 diabetes in a glucose lowering-independent way. Most of the observed changes can be considered beneficial and may contribute to the renoprotective properties of dapagliflozin.

Indexed as

AgedBenzhydryl CompoundsBlood GlucoseDiabetes Mellitus, Type 2FemaleGlucosidesGlycated HemoglobinGreeceHumansMaleMetabolomeMetforminMiddle AgedTreatment OutcomeUrinalysisBenzhydryl CompoundsBlood GlucosedapagliflozinGlucosidesGlycated HemoglobinMetforminbranched chain amino acidsdapagliflozinkidneymetabolomicsosmolytes

Identifiers

PMID33592103
PMCPMC8063232
OpenAlexW3131824613

What Socratic holds

Textfull text, public
LicenceCC BY
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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 Socratic graph.