Systemic evaluation of the effects of monomeric GLP-1R-based agonists on MASLD and its complications.

ABSTRACT:

Background

Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most common chronic liver disease worldwide, yet efficient therapeutic approaches are lacking. The advent of glucagon-like peptide-1 receptor (GLP-1R)-based multi-target agonists generated renewed optimism for MASLD. Building on preclinical and clinical data suggesting synergistic metabolic benefits, we hypothesized that combining glucose-dependent insulinotropic polypeptide receptor (GIPR) or glucagon receptor (GCGR) agonism with GLP-1R agonism would confer superior protective effects against MASLD and its complications.

Methods

We identified genetic proxies of the effect of GLP-1R, GIPR, and GCGR by combining Mendelian randomization (MR), Bayesian colocalization, and linkage disequil

SUBMITTER: Cai Y 

PROVIDER: S-EPMC12305972 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature