A Long-Acting PYY_3-36 Analog Mediates Robust Anorectic Efficacy with Minimal Emesis in Nonhuman Primates.

ABSTRACT: The gut hormone PYY_3-36 reduces food intake in humans and exhibits at least additive efficacy in combination with GLP-1. However, the utility of PYY analogs as anti-obesity agents has been severely limited by emesis and rapid proteolysis, a profile similarly observed with native PYY_3-36 in obese rhesus macaques. Here, we found that antibody conjugation of a cyclized PYY_3-36 analog achieved high NPY2R selectivity, unprecedented in vivo stability, and gradual infusion-like exposure. These properties permitted profound reduction of food intake when administered to macaques for 23 days without a single emetic event in any animal. Co-administration with the GLP-1 receptor agonist liraglutide for an additional 5 days further reduced food intake with only one anim

SUBMITTER: Rangwala SM 

PROVIDER: S-EPMC6701930 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature