Asian subpopulations may exhibit greater cardiovascular benefit from long-acting glucagon-like peptide 1 receptor agonists: A meta-analysis of cardiovascular outcome trials

Yu Mi Kang, Yun Kyung Cho, Jiwoo Lee, Seung Eun Lee, Woo Je Lee, Joong Yeol Park, Ye Jee Kim, Chang Hee Jung, Michael A. Nauck

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Background: Based on reported results of three large cardiovascular outcome trials (CVOTs) of glucagon-like peptide 1 receptor agonists (GLP-1 RAs), we aimed to investigate the overall effect of GLP-1 RAs on major adverse cardiovascular events (MACEs) and to identify subpopulations exhibiting the greatest cardiovascular (CV) benefit. Methods: Three CVOTs reporting effects of long-acting GLP-1 RAs were included: LEADER (liraglutide), SUSTAIN-6 (semaglutide), and EXSCEL (exenatide once weekly). In all studies, the primary endpoint was three-point MACE, comprising CV death, non-fatal myocardial infarction, and non-fatal stroke. Overall effect estimates were calculated as hazard ratios and 95% confidence intervals (CIs) using the random-effects model; subgroup analyses reported in the original studies were similarly analyzed. Results: Overall, statistically significant risk reductions in MACE and CV death were observed. Subgroup analysis indicated a significant racial difference with respect to CV benefit (P for interaction <0.001), and more substantial risk reductions were observed in subjects of African origin (relative risk [RR], 0.78; 95% CI, 0.60 to 0.99) and in Asians (RR, 0.35; 95% CI, 0.09 to 1.32). However, post hoc analysis (Bonferroni method) revealed that only Asians exhibited a significantly greater CV benefit from treatment, compared with white subjects (P<0.0001). Conclusion: Long-acting GLP-1 RAs reduced risks of MACE and CV deaths in high-risk patients with type 2 diabetes mellitus. Our findings of a particularly effective reduction in CV events with GLP-1 RA in Asian populations merits further exploration and dedicated trials in specific populations.

Original languageEnglish
Pages (from-to)410-421
Number of pages12
JournalDiabetes and Metabolism Journal
Volume43
Issue number4
DOIs
StatePublished - 1 Aug 2019

Keywords

  • Agonist
  • Cardiovascular disease
  • Diabetes mellitus, type 2
  • Glucagon-like peptide 1
  • Incretins
  • Meta-analysis
  • Safety
  • Therapeutics

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