Diabetes Metab J.  2019 Aug;43(4):410-421. 10.4093/dmj.2018.0070.

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

• Kang YM
• Cho YK
• Lee J
• Lee SE
• Lee WJ
• Park JY
• Kim YJ
• Jung CH
• Nauck MA

• KMID: 2455665
• DOI: http://doi.org/10.4093/dmj.2018.0070

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.

Keyword

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

MeSH Terms

Asian Continental Ancestry Group*
Cardiovascular Diseases
Diabetes Mellitus, Type 2
Glucagon-Like Peptide 1*
Humans
Incretins
Myocardial Infarction
Stroke
Glucagon-Like Peptide 1
Incretins

Figure

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  Fig. 1 The composite analysis of the risk of major adverse cardiovascular events (MACEs) from three cardiovascular outcome trials, expressed as relative risk (RR): (A) three-point MACE, (B) cardiovascular death, (C) non-fatal myocardial infarction, and (D) non-fatal stroke. CI, confidence interval; GLP-1, glucagon-like peptide 1; LEADER, Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results; SUSTAIN-6, Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes; EXSCEL, Exenatide Study of Cardiovascular Event Lowering Trial.

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  Fig. 2 The combined subgroup analysis of the risk of major adverse cardiovascular events from three cardiovascular outcome trials. RR, relative risk; CI, confidence interval; GLP-1 RA, glucagon-like peptide 1 receptor agonist; HbA1c, glycosylated hemoglobin; CVD, cardiovascular disease.

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