The Design of a GLP‐1/PYY Dual Acting Agonist

Abstract

The two gut hormones GLP-1 and PYY 3-36 ,w hich are both secreted from the L-cells upon food stimuli, have as tronger inhibitory effect on food intake when they are combined, compared to their individual effects as single agonists.A lthough they are not homologous and share no sequence similarity,w es howt hat aG LP-1 analogue can be designed to exhibit potent activity on both the Y 2 and GLP-1r eceptors.D ual acting hybrid analogues were realized by designing truncated and potent Y 2 receptor PYY analogues, followed by integrating the critical residues into GLP-1. In this study,w es how that one of these dual acting agonists acutely reduces food intake significantly more than the respective mono-agonist counterparts.