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Diabetes Metab J. 2018 Dec 27. doi: 10.4093/dmj.2018.0070. [Epub ahead of print]

Asian Subpopulations May Exhibit Greater Cardiovascular Benefit from Long-Acting Glucagon-Like Peptide 1 Receptor Agonists: A Meta-Analysis of Cardiovascular Outcome Trials.

Author information

1
International Healthcare Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
2
Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
3
Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
4
Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. chjung0204@amc.seoul.kr.
5
Diabetes Center Bochum-Hattingen, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany. Michael.nauck@rub.de.
#
Contributed equally

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.

KEYWORDS:

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

PMID:
30604598
DOI:
10.4093/dmj.2018.0070
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Conflict of interest statement

Michael A. Nauck has been member on advisory boards or has consulted with AstraZeneca, Boehringer Ingelheim, Eli Lilly & Co., Fractyl, GlaxoSmithKline, Menarini/Berlin Chemie, Merck, Sharp & Dohme, and NovoNordisk. He has received grant support from AstraZeneca, Eli Lilly & Co., Menarini/Berlin-Chemie, Merck, Sharp & Dohme, Novartis Pharma, and NovoNordisk. He has also served on the speakers' bureau of AstraZeneca, Boehringer Ingelheim, Eli Lilly % Co., Menarini/Berlin Chemie, Merck, Sharp % Dohme, and NovoNordisk.

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