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Upon binding to GLP-1 receptors, GLP-1 RAs activate G-protein signaling pathways, leading to increased cyclic AMP and activation of protein kinase A, which in turn enhances insulin biosynthesis and suppresses glucagon secretion 13,14,15

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Recently, it has been reported intraperitoneal administration of GLP-1RA activates mesenteric ganglia located periphery to the IML and inhibits intestinal motility 40 ,which is consistent with our results

The synergy arises because metformin reduces hunger-signaling hormones while semaglutide enhances satiety