A glycosylated Fc-fused glucagon-like peptide-1 receptor agonist exhibits equivalent glucose lowering to but fewer gastrointestinal side effects than dulaglutide.

ABSTRACT:

Aim

To evaluate the pharmacokinetic and pharmacodynamic properties of a novel glycosylated Fc-fused glucagon-like peptide-1(GLP-1-gFc) receptor agonist with distinctive receptor binding affinity, designed to improve in vivo stability and safety relative to the commercial GLP-1 analogue dulaglutide, and assess its safety profile and pharmacokinetics in healthy humans.

Materials and methods

We constructed GLP-1-gFc and determined its binding affinity and potency using in vitro instrumental and cell-based analyses followed by in vivo comparison of the glucose-lowering and gastrointestinal side effects between GLP-1-gFc and dulaglutide. A phase 1 clinical trial was conducted to confirm the efficacy and safety profile of GLP-1-gFc.

Results

GLP-1-gFc showed 10-fold less bin

SUBMITTER: An IB 

PROVIDER: S-EPMC7383507 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature