Evidence map›Paper›PMID 34558768›Full record

Trial reportDiabetes, obesity & metabolism2022

Empagliflozin and uric acid metabolism in diabetes: A post hoc analysis of the EMPA-REG OUTCOME trial.

João Pedro Ferreira, Silvio E Inzucchi, Michaela Mattheus, Thomas Meinicke, Dominik Steubl, Christoph Wanner, Bernard Zinman

Registry-linked trialOpen access · hybridAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Diabetes, obesity & metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01131676 (A Phase III, Multicentre, International, Randomised, Parallel Group, Double Blind Cardiovascular Safety Study of BI 10773), which is not on this map. Cited by 40 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 2 pooled it
6.9field-weighted citation impact, top 2% 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.

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
3 · Its place in the literature

Who cites it

40 citing papers in PubMed, 2 syntheses or guidelines pooled it, 61 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Extrapolated longer-term effects of the DAPA-CKD trial: a modelling analysis.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2023
    Trial
  5. Trial
  6. Trial
  7. Trial
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Review
  19. Article
  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

7 authors at 5 institutions in 5 countries.

João Pedro FerreiraUniversité de Lorraine, Centre d'Investigations Cliniques Plurithématique 1433 and Inserm U1116, Centre Hospitalier Universitaire de Nancy, FCRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France.ORCID 0000-0002-2304-6138
Silvio E InzucchiSection of Endocrinology, Yale School of Medicine and Yale-New Haven Hospital, New Haven, Connecticut, USA.ORCID 0000-0003-1254-6636
Michaela MattheusBoehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany.
Thomas MeinickeBoehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany.
Dominik SteublBoehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany.
Christoph WannerDepartment of Medicine, Division of Nephrology, Würzburg University Clinic, Würzburg, Germany.
Bernard ZinmanLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.ORCID 0000-0002-0041-1876
Boehringer Ingelheim (Germany) · DEInserm · FRLunenfeld-Tanenbaum Research Institute · CAUniversity of Würzburg · DEYale New Haven Hospital · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimTo evaluate the effect of empagliflozin on uric acid (UA) levels, antigout medication and gout episodes in the EMPA-REG OUTCOME trial (NCT01131676). MATERIALS AND

methodsA total of 7020 patients with type 2 diabetes (T2D) were randomized to either empagliflozin (10 or 25 mg) or placebo. The effects of empagliflozin versus placebo on UA concentration were assessed using mixed linear models. A composite outcome of new prescription of antigout medication or gout episode was studied with Cox proportional hazards models.

resultsEmpagliflozin reduced serum UA levels versus placebo: week 52 adjusted mean treatment difference = -0.37 (95% confidence interval [CI] -0.42, -0.31) mg/dL; this was more pronounced in patients with baseline UA ≥ 7.0 mg/dL versus <7.0 mg/dL: week 52 adjusted mean treatment difference = -0.56 (95% CI -0.68, -0.43) and -0.30 (95% CI -0.37, -0.24) mg/dL, respectively. Among 6607 patients not taking antigout medications at baseline, 5.2% had a gout episode or initiated antigout treatment versus 3.6% in the placebo and empagliflozin groups, respectively: hazard ratio 0.67 (95% CI 0.53, 0.85; P = 0.001). Both components of the composite outcome contributed to the reduction with empagliflozin in the composite. Risk reduction was similar with both empagliflozin doses.

conclusionsEmpagliflozin reduced UA levels and the composite of gout episodes or prescription of antigout medication. These clinically important findings expand the utility of empagliflozin as a potential antigout treatment in patients with T2D, beyond its well-established cardio-renal benefits.

Indexed as

Cardiovascular DiseasesDiabetes Mellitus, Type 2Benzhydryl CompoundsGlucosidesHumansHypoglycemic AgentsTreatment OutcomeUric AcidBenzhydryl CompoundsempagliflozinGlucosidesHypoglycemic AgentsUric Acidantigout treatmentempagliflozingouttype 2 diabetesuric acid

Identifiers

PMID34558768
PMCPMC9293326
OpenAlexW3199674324

What Socratic holds

Textmetadata
LicenceCC BY-NC
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.