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doi:10.1080/14656566.2017.1381086 25

Adverse events in the trial mostly aligned with established drug profiles, with no new safety concerns

glucagon-like peptide-1 receptor agonists (GLP-1 RAs) ( 1) 1 GLP-1 RAs 1 GLP-1 RAs 2 GLP-1 Receptor GLP-1 Receptor (GLP-1R) (pleiotropic effects) GLP-1 RAs GLP-1R GLP-1R : GLP-1R (-cells) GLP-1 (glucose-dependent insulinotropic action) : GLP-1R sinoatrial node 2 10 GLP-1 RAs : GLP-1R paraventricular nucleus arcuate nucleus hypothalamus, nucleus tractus solitarius area postrema : GLP-1R (natriuresis) (nephroprotection) : GLP-1R Brunners glands myenteric plexus macrophages T cells GLP-1RAs (atherosclerosis): GLP-1R atherosclerotic plaques GLP-1R macrophages macrophages foam cells : nitric oxide (NO) : GLP-1RAs atherosclerotic plaques Nuclear Factor-B (NF-B): Interleukin-6 (IL_6) Tumor Necrosis Factor-alpha (TNF- ) macrophage (macrophage polarization): macrophage M1 M2 : GLP-1R (tubular cells) podocyte ferroptosis: GLP-1 RAs ferroptosis ferroptosis : GLP-1 RAs Transforming growth factor-(TGF-) : (natriuresis) (hyperfiltration) GLP-1 RAs SGLT2 inhibitors GLP-1 RAs Sodium-glucose cotransporter-2 (SGLT-2) inhibitors LEADER: liraglutide MACE ( ) 13 22 15 SUSTAIN-6: semaglutide MACE 26 39 HARMONY Outcomes: albiglutide MACE 22 6 REWIND: dulaglutide (primary prevention) 31 dulaglutide MACE 12 (4 ) FLOW trial: semaglutide semaglutide 24 (eGFR) GLP-1 RAs LEADER HbA1c (urinary albumin-creatinine ratio

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