A Long-Acting FGF21 Molecule, PF-05231023, Decreases Body Weight and Improves Lipid Profile in Non-human Primates and Type 2 Diabetic Subjects

作者：Talukdar Saswata^*; Zhou Yingjiang; Li Dongmei; Rossulek Michelle; Dong Jennifer; Somayaji Veena; Weng Yan; Clark Ronald; Lanba Adhiraj; Owen Bryn M; Brenner Martin B; Trimmer Jeffrey K; Gropp Kathryn E; Chabot Jeffrey R; Erion Derek M; Rolph Timothy P; Goodwin Bryan; Calle Roberto A^*

来源：Cell Metabolism, 2016, 23(3): 427-440.

DOI：10.1016/j.cmet.2016.02.001

FGF21 plays a central role in energy, lipid, and glucose homeostasis. To characterize the pharmacologic effects of FGF21, we administered a longacting FGF21 analog, PF-05231023, to obese cynomolgus monkeys. PF-05231023 caused a marked decrease in food intake that led to reduced body weight. To assess the effects of PF-05231023 in humans, we conducted a placebo-controlled, multiple ascending-dose study in overweight/obese subjects with type 2 diabetes. PF-05231023 treatment resulted in a significant decrease in body weight, improved plasma lipoprotein profile, and increased adiponectin levels. Importantly, there were no significant effects of PF-05231023 on glycemic control. PF-05231023 treatment led to dose-dependent changes in multiple markers of bone formation and resorption and elevated insulin-like growth factor 1. The favorable effects of PF-05231023 on body weight support further evaluation of this molecule for the treatment of obesity. Longer studies are needed to assess potential direct effects of FGF21 on bone in humans.

• 出版日期2016-3-8