Douros Jonathan D, Mowery Stephanie A, Knerr Patrick J
Indiana Biosciences Research Institute, Indianapolis, IN 46202, USA.
J Clin Med. 2025 May 29;14(11):3812. doi: 10.3390/jcm14113812.
Emerging clinical data support the paradoxical notion that glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) agonism and antagonism can provide additive weight loss when combined with a glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) agonist. In this review, we examine data that motivated the initiation of these seemingly contradictory drug discovery programs. We focus on the physiologic role of GIP in humans, human genetics evidence, rodent genetic models, and preclinical rodent and non-human primate pharmacology studies. Furthermore, we highlight where early preclinical findings translated into relevant clinical efficacy in the development of tirzepatide and maridebart cafraglutide (MariTide).
葡萄糖依赖性促胰岛素多肽（GIP）受体（GIPR）激动剂和拮抗剂与胰高血糖素样肽1（GLP-1）受体（GLP-1R）激动剂联合使用时，可带来额外的体重减轻。在本综述中，我们研究了推动启动这些看似相互矛盾的药物研发项目的数据。我们重点关注GIP在人类中的生理作用、人类遗传学证据、啮齿动物遗传模型以及临床前啮齿动物和非人类灵长类动物的药理学研究。此外，我们还强调了在替尔泊肽和玛仕德肽（MariTide）的研发过程中，早期临床前研究结果转化为相关临床疗效的情况。
