Heterogeneity Amongst GLP-1 RA Cardiovascular Outcome Trials Results: Can Definition of Established Cardiovascular Disease Be the Missing Link?

Detalhes bibliográficos
Autor(a) principal: Melo, M
Data de Publicação: 2021
Outros Autores: Gavina, C, Silva-Nunes, J, Andrade, L, Carvalho, D
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.17/3779
Resumo: Atherosclerotic cardiovascular diseases are the leading cause of adverse outcomes in patients with type 2 diabetes, and all new anti-diabetic agents are mandated to undergo cardiovascular outcome trials (CVOTs). Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are incretin mimetics that reduce blood glucose levels with a low associated risk of hypoglycaemia. CVOTs with different GLP-1 RAs yielded different results in terms of major cardiovascular composite outcome (MACE), with some trials showing superiority in the treatment arm, whereas other simply displayed non-inferiority. More importantly, the significance of each component of MACE varied between drugs. This begs the question of whether these differences are due to dissimilarities between drugs or other factors, namely trial design, are at the root of these differences. We analyse the trial designs for all CVOTs with GLP-1 RAs and highlight important differences between them, namely in terms of definition of established cardiovascular disease, and discuss how these differences might explain the disparate results of the trials and preclude direct comparisons between them. We conclude that a fair comparison between GLP-1 RA CVOTs would involve post-hoc analysis re-grouping the patients into different cardiovascular risk categories based upon their baseline clinical parameters, in order to even out the criteria used to classify patients.
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spelling Heterogeneity Amongst GLP-1 RA Cardiovascular Outcome Trials Results: Can Definition of Established Cardiovascular Disease Be the Missing Link?HCC ENDAntidiabetic DrugGLP-1 RACardiovascular DiseaseCardiovascular Outcome TrialsType 2 DiabetesAtherosclerotic cardiovascular diseases are the leading cause of adverse outcomes in patients with type 2 diabetes, and all new anti-diabetic agents are mandated to undergo cardiovascular outcome trials (CVOTs). Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are incretin mimetics that reduce blood glucose levels with a low associated risk of hypoglycaemia. CVOTs with different GLP-1 RAs yielded different results in terms of major cardiovascular composite outcome (MACE), with some trials showing superiority in the treatment arm, whereas other simply displayed non-inferiority. More importantly, the significance of each component of MACE varied between drugs. This begs the question of whether these differences are due to dissimilarities between drugs or other factors, namely trial design, are at the root of these differences. We analyse the trial designs for all CVOTs with GLP-1 RAs and highlight important differences between them, namely in terms of definition of established cardiovascular disease, and discuss how these differences might explain the disparate results of the trials and preclude direct comparisons between them. We conclude that a fair comparison between GLP-1 RA CVOTs would involve post-hoc analysis re-grouping the patients into different cardiovascular risk categories based upon their baseline clinical parameters, in order to even out the criteria used to classify patients.BMCRepositório do Centro Hospitalar Universitário de Lisboa Central, EPEMelo, MGavina, CSilva-Nunes, JAndrade, LCarvalho, D2021-07-29T14:17:13Z20212021-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.17/3779engDiabetol Metab Syndr. 2021 Jul 27;13(1):81.10.1186/s13098-021-00698-5.info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-10-28T10:29:41Zoai:repositorio.chlc.pt:10400.17/3779Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-10-28T10:29:41Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Heterogeneity Amongst GLP-1 RA Cardiovascular Outcome Trials Results: Can Definition of Established Cardiovascular Disease Be the Missing Link?
title Heterogeneity Amongst GLP-1 RA Cardiovascular Outcome Trials Results: Can Definition of Established Cardiovascular Disease Be the Missing Link?
spellingShingle Heterogeneity Amongst GLP-1 RA Cardiovascular Outcome Trials Results: Can Definition of Established Cardiovascular Disease Be the Missing Link?
Melo, M
HCC END
Antidiabetic Drug
GLP-1 RA
Cardiovascular Disease
Cardiovascular Outcome Trials
Type 2 Diabetes
title_short Heterogeneity Amongst GLP-1 RA Cardiovascular Outcome Trials Results: Can Definition of Established Cardiovascular Disease Be the Missing Link?
title_full Heterogeneity Amongst GLP-1 RA Cardiovascular Outcome Trials Results: Can Definition of Established Cardiovascular Disease Be the Missing Link?
title_fullStr Heterogeneity Amongst GLP-1 RA Cardiovascular Outcome Trials Results: Can Definition of Established Cardiovascular Disease Be the Missing Link?
title_full_unstemmed Heterogeneity Amongst GLP-1 RA Cardiovascular Outcome Trials Results: Can Definition of Established Cardiovascular Disease Be the Missing Link?
title_sort Heterogeneity Amongst GLP-1 RA Cardiovascular Outcome Trials Results: Can Definition of Established Cardiovascular Disease Be the Missing Link?
author Melo, M
author_facet Melo, M
Gavina, C
Silva-Nunes, J
Andrade, L
Carvalho, D
author_role author
author2 Gavina, C
Silva-Nunes, J
Andrade, L
Carvalho, D
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Repositório do Centro Hospitalar Universitário de Lisboa Central, EPE
dc.contributor.author.fl_str_mv Melo, M
Gavina, C
Silva-Nunes, J
Andrade, L
Carvalho, D
dc.subject.por.fl_str_mv HCC END
Antidiabetic Drug
GLP-1 RA
Cardiovascular Disease
Cardiovascular Outcome Trials
Type 2 Diabetes
topic HCC END
Antidiabetic Drug
GLP-1 RA
Cardiovascular Disease
Cardiovascular Outcome Trials
Type 2 Diabetes
description Atherosclerotic cardiovascular diseases are the leading cause of adverse outcomes in patients with type 2 diabetes, and all new anti-diabetic agents are mandated to undergo cardiovascular outcome trials (CVOTs). Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are incretin mimetics that reduce blood glucose levels with a low associated risk of hypoglycaemia. CVOTs with different GLP-1 RAs yielded different results in terms of major cardiovascular composite outcome (MACE), with some trials showing superiority in the treatment arm, whereas other simply displayed non-inferiority. More importantly, the significance of each component of MACE varied between drugs. This begs the question of whether these differences are due to dissimilarities between drugs or other factors, namely trial design, are at the root of these differences. We analyse the trial designs for all CVOTs with GLP-1 RAs and highlight important differences between them, namely in terms of definition of established cardiovascular disease, and discuss how these differences might explain the disparate results of the trials and preclude direct comparisons between them. We conclude that a fair comparison between GLP-1 RA CVOTs would involve post-hoc analysis re-grouping the patients into different cardiovascular risk categories based upon their baseline clinical parameters, in order to even out the criteria used to classify patients.
publishDate 2021
dc.date.none.fl_str_mv 2021-07-29T14:17:13Z
2021
2021-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
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dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.17/3779
url http://hdl.handle.net/10400.17/3779
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Diabetol Metab Syndr. 2021 Jul 27;13(1):81.
10.1186/s13098-021-00698-5.
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eu_rights_str_mv openAccess
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dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv mluisa.alvim@gmail.com
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