Heterogeneity amongst GLP-1 RA cardiovascular outcome trials results: can definition of established cardiovascular disease be the missing link?

Diabetology & Metabolic Syndrome

Cristina Gavina¹  Luís Andrade²  Miguel Melo³  José Silva-Nunes⁴  Davide Carvalho⁵ 

[1] Cardiology Department, Hospital Pedro Hispano-ULS Matosinhos, Matosinhos, Portugal;Cardiovascular Research and Development Unit, Faculty of Medicine, Universidade do Porto, Porto, Portugal;Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar E Universitário S. João, Porto, Portugal;Centro Hospitalar de Vila Nova de Gaia-Espinho, Vila Nova de Gaia, Portugal;Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar E Universitário S. João, Porto, Portugal;Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar e Universitário de Coimbra, Praceta, R. Prof. Mota Pinto, 3004-561, Coimbra, Portugal;Faculty of Medicine, Universidade de Coimbra, Coimbra, Portugal;Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar E Universitário S. João, Porto, Portugal;Department of Endocrinology, Diabetes, and Metabolism, Centro Hospitalar Universitário de Lisboa Central, Lisboa, Portugal;NOVA Medical School / Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisboa, Portugal;Health and Technology Research Center (H&TRC), Escola Superior de Tecnologia da Saúde de Lisboa, Lisboa, Portugal;Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar E Universitário S. João, Porto, Portugal;Faculty of Medicine, Universidade do Porto, Porto, Portugal;i3SInstituto de Investigação e Inovação Em Saúde, Universidade do Porto, Porto, Portugal;Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar E Universitário S. João, Porto, Portugal;

关键词: Antidiabetic drug;    GLP-1 RA;    Cardiovascular disease;    Cardiovascular outcome trials;    Type 2 diabetes;   

DOI  :  10.1186/s13098-021-00698-5

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY