A metabolic comparison of GIPR agonism versus GIPR antagonism in male mice.

ABSTRACT:

Aims

Targeting the glucose dependent insulinotropic polypeptide receptor (GIPR) is of growing interest for treating type 2 diabetes and obesity, though the optimal approach remains unclear. Both GIPR agonism and antagonism, respectively, incorporated into drugs like tirzepatide and maridebart cafraglutide, have paradoxically both shown significant weight loss effects in humans.

Materials and methods

In this study, the metabolic impacts of a GIPR agonist (GIP108) and antagonist (NN-GIPR-Ant) were evaluated in lean and high-fat diet (HFD)-induced obese male mice. We assessed the impacts on food intake, body weight, glucose and insulin tolerance, liver triglyceride levels, bone markers and adipose tissue lipolytic gene expression.

Results

In lean mice, neither peptide af

SUBMITTER: Davies I 

PROVIDER: S-EPMC12803606 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature