Long-acting GLP-1 receptor agonists are associated with a reduction in (MACE) and cardiovascular deaths.
Statistically significant reductions in MACE and cardiovascular death were observed across three large cardiovascular outcome trials.
A notable racial difference in cardiovascular benefit was identified, with stronger effects in subjects of African origin and Asians.
Asians showed a significant reduction in cardiovascular events compared to white subjects, indicating a potential differential response to treatment.
Further exploration and dedicated trials in specific populations may be warranted to understand the observed effects.
Simplified
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 (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 (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,analysis (Bonferroni method) revealed that only Asians exhibited a significantly greater CV benefit from treatment, compared with white subjects (<0.0001). P post hoc P
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.
Key numbers
0.88
Risk Reduction
Relative risk (RR) of from combined analysis of three CVOTs.
0.85
Cardiovascular Death Risk Reduction
Relative risk (RR) for cardiovascular death from combined analysis.
0.35
Asian Population Benefit
Relative risk (RR) for Asians receiving GLP-1 RAs.
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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.
