Evidence mapPaperPMID 35933413Full record

Trial reportCardiovascular diabetology2022

Evolocumab on top of empagliflozin improves endothelial function of individuals with diabetes: randomized active-controlled trial.

Andrei C Sposito, Ikaro Breder, Joaquim Barreto, Jessica Breder, Isabella Bonilha, Marcus Lima, Alessandra Oliveira, Vaneza Wolf, Beatriz Luchiari, Helison R do Carmo and 11 more

Open access · goldFull text readRandomized Controlled Trial
In one paragraph

Trial report in Cardiovascular diabetology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.2field-weighted citation impact, top 11% 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

13 citing papers in PubMed, 20 citations in OpenAlex.

  1. PCSK-9-inhibitor therapy improves endothelial function in high-risk patients with cardiovascular disease.Clinical research in cardiology : official journal of the German Cardiac Society · 2026
    Trial
  2. Trial
  3. Article
  4. Endothelial Metabolic Reprogramming Links Diabetes to Atherosclerosis.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026
    Review
  5. Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. The Anti-Thrombotic Effects of PCSK9 Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2023
    Review
  13. Review
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

21 authors at 2 institutions in 2 countries.

Andrei C SpositoDivision of Cardiology, State University of Campinas (Unicamp), Campinas, Sao Paulo, 13084-971, Brazil. sposito@unicamp.com.
Ikaro BrederDivision of Cardiology, State University of Campinas (Unicamp), Campinas, Sao Paulo, 13084-971, Brazil.
Joaquim BarretoDivision of Cardiology, State University of Campinas (Unicamp), Campinas, Sao Paulo, 13084-971, Brazil.
Jessica BrederDivision of Cardiology, State University of Campinas (Unicamp), Campinas, Sao Paulo, 13084-971, Brazil.
Isabella BonilhaDivision of Cardiology, State University of Campinas (Unicamp), Campinas, Sao Paulo, 13084-971, Brazil.
Marcus LimaDivision of Cardiology, State University of Campinas (Unicamp), Campinas, Sao Paulo, 13084-971, Brazil.
Alessandra OliveiraDivision of Cardiology, State University of Campinas (Unicamp), Campinas, Sao Paulo, 13084-971, Brazil.
Vaneza WolfDivision of Cardiology, State University of Campinas (Unicamp), Campinas, Sao Paulo, 13084-971, Brazil.
Beatriz LuchiariDivision of Cardiology, State University of Campinas (Unicamp), Campinas, Sao Paulo, 13084-971, Brazil.
Helison R do CarmoDivision of Cardiology, State University of Campinas (Unicamp), Campinas, Sao Paulo, 13084-971, Brazil.
Daniel MunhozDivision of Cardiology, State University of Campinas (Unicamp), Campinas, Sao Paulo, 13084-971, Brazil.
Daniela OliveiraDivision of Cardiology, State University of Campinas (Unicamp), Campinas, Sao Paulo, 13084-971, Brazil.
Otavio R Coelho-FilhoDivision of Cardiology, State University of Campinas (Unicamp), Campinas, Sao Paulo, 13084-971, Brazil.
Otavio R CoelhoDivision of Cardiology, State University of Campinas (Unicamp), Campinas, Sao Paulo, 13084-971, Brazil.
Jose Roberto Matos-SouzaDivision of Cardiology, State University of Campinas (Unicamp), Campinas, Sao Paulo, 13084-971, Brazil.
Filipe A MouraDivision of Cardiology, State University of Campinas (Unicamp), Campinas, Sao Paulo, 13084-971, Brazil.
Luiz Sergio F de CarvalhoDivision of Cardiology, State University of Campinas (Unicamp), Campinas, Sao Paulo, 13084-971, Brazil.
Wilson NadruzDivision of Cardiology, State University of Campinas (Unicamp), Campinas, Sao Paulo, 13084-971, Brazil.
Thiago QuinagliaDivision of Cardiology, State University of Campinas (Unicamp), Campinas, Sao Paulo, 13084-971, Brazil.
Sheila T Kimura-MedorimaDivision of Cardiology, State University of Campinas (Unicamp), Campinas, Sao Paulo, 13084-971, Brazil.
EXCEED-BHS3 Group
Universidade Estadual de Campinas (UNICAMP) · BRHarvard University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSodium-glucose cotransporter 2 inhibitors (SGLT2i) improve endothelial dysfunction and reduce cardiovascular events in individuals with type 2 diabetes (T2D). Proprotein convertase subtilisin/kexin 9 (PCSK9i) inhibitors reduce cardiovascular events in high-risk patients. Whether the addition of PCSK9i to SGLT2i treatment adds benefits is not known.

objectivesTo assess the PCSK9-i effect on the endothelial function of T2D individuals under treatment with SGLT2-i.

methodsIndividuals with T2D were randomized in a 1:1 ratio to a 16-week treatment with either empagliflozin (E) or empagliflozin plus evolocumab (EE). The primary endpoint was post-treatment change from baseline in flow-mediated dilation (FMD) at 1-min. Secondary outcomes included changes in plasma levels of nitric oxide metabolites and isoprostane.

resultsA total of 110 patients were enrolled, the mean age was 58 years, and 71% were men. The median post-treatment change in FMD at 1-min was 2.7% (interquartile range [IQR]: 0.9%) and 0.4% (IQR: 0.9%) in the EE and E groups, respectively (p < 0.001). There was a greater increase in plasma levels of nitrate [5.9 (16.5) vs. 2.6 (11.8); p = 0.001] and nitrite [0.14 (0.72) vs. 0.02 (0.74); p = 0.025] in the EE group than in the E group, respectively. Isoprostane reduction was more pronounced in the EE group when compared to the E group [-1.7 (5.9) vs. -1.1 (5.3); p < 0.001).

conclusionsIn individuals with T2D, the addition of evolocumab on top of empagliflozin improves endothelial function.

Indexed as

Cardiovascular DiseasesDiabetes Mellitus, Type 2Antibodies, Monoclonal, HumanizedBenzhydryl CompoundsFemaleGlucosidesHumansIsoprostanesMaleMiddle AgedPCSK9 InhibitorsProprotein Convertase 9Treatment OutcomeAntibodies, Monoclonal, HumanizedBenzhydryl CompoundsempagliflozinevolocumabGlucosidesIsoprostanesPCSK9 InhibitorsPCSK9 protein, humanProprotein Convertase 9Endothelial dysfunctionFlow-mediated dilationPCSK9i

Identifiers

PMID35933413
PMCPMC9356512
OpenAlexW4290001009

What Socratic holds

Textfull text, public
LicenceCC BY
Read underepoch 390

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 Socratic graph.