• Shuzhen Bai, Chu Lin, Ruoyang Jiao, Xiaoling Cai, Suiyuan Hu, Fang Lv, Wenjia Yang, Xingyun Zhu, and Linong Ji.
• Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China.
• Eur. J. Intern. Med. 2023 Mar 1; 109: 798879-88.

ImportanceDisparities were found in the cardiovascular and renal outcomes among different glucagon-like peptide 1 receptor agonist (GLP-1RA) subtypes. However, whether the characteristics of GLP-1RA itself are associated with these disparities remains unclear.ObjectiveTo assess the association between the steady-state concentration, duration of action, or molecular weight of GLP-1RA and the risks of cardiovascular and renal outcomes in patients with type 2 diabetes (T2D).Data SourcesPubMed, MEDLINE, EMBASE, Cochrane and Clinicaltrial.gov from inception to April 2022.Study SelectionRandomized controlled trials (RCTs) investigating GLP-1RAs in patients with T2D were included.Data Extraction And SynthesisLiterature screening and data extraction were performed independently by 2 researchers. The outcomes were computed as odds ratio (OR) and its 95% confidence interval (CI). Subgroup analyses were conducted according to steady-state concentration, duration of action and molecular weight of GLP-1RAs.Main Outcomes And MeasuresPrimary outcomes were major adverse cardiovascular events (MACE), composite renal outcome and all-cause mortality.ResultsIn all, 61 RCTs were included. When compared with non-GLP-1RA agents, GLP-1RAs with high steady-state concentration were associated with greater risk reduction in MACE (p for subgroup difference = 0.01) and the composite renal outcome (p for subgroup difference = 0.008) in patients with T2D. Greater risk reductions in MACE between GLP-1RA users versus non-GLP-RA users were observed in long acting stratum when compared with short acting stratum (p for subgroup difference = 0.04) in patients with T2D. The molecular weight of GLP-1RAs was not associated with the risk of cardiovascular and renal outcomes.Conclusions And RelevanceGLP-1RAs with high steady-state concentrations might be associated with greater risk reductions in cardiovascular and renal outcomes in patients with T2D. Long acting GLP-1RAs might outperform short acting ones in reducing the risk of cardiovascular outcomes. These findings provided new insights for guiding the clinical applications of GLP-1RAs in patients with T2D.Copyright © 2023. Published by Elsevier B.V.

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