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Peripheral effects Via the AMY2 and AMY3 receptors Cagrilintide acts peripherally: Slowing of gastric emptying , stronger than with GLP-1 Suppression of postprandial glucagon , helps control postprandial glycemic spikes Modulation of bone remodeling (via AMY3), a neutral effect, but clinically monitored Synergy with GLP-1 (the mechanistic basis of CagriSema) The main innovation is the complementarity with the GLP-1 pathway : GLP-1 suppresses appetite via the arcuate nucleus of the hypothalamus (POMC neurons, AgRP/NPY inhibition) Amylin suppresses appetite via the area postrema (CGRP-like neurons) Two independent centers, two independent mechanisms

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Front Immunol 9:3081 Hayasaka H et al (2010) Neogenesis and development of the high endothelial venules that mediate lymphocyte trafficking

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