GLP1R and GIPR Dual-Target Drugs in Humanized GIPR Mice

Multi-target drugs targeting GLP1R/GIPR/GCGR have demonstrated superior efficacy for weight loss and glycemic control compared to single-target GLP1R drugs. However, due to limitations in sequence homology, some GIPR-targeting drugs developed in rodents may not translate as effectively to humans as GLP-1R drugs.

To overcome this limitation and improve the translational relevance of preclinical studies, WuXi Biology scientists employed GIPR-humanized mice, in which the murine GIPR gene is replaced with its human counterpart. Using this model, the authors presented a poster at the Obesity Week 2025 conference highlighting a case study evaluating the weight-loss efficacy of tirzepatide and AMG133, showing that both drugs exhibited significantly enhanced anti-obesity effects in GIPR-humanized mice compared to wild-type diet-induced obesity (DIO) mice.