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

Cell Metab. 2016 Mar 8;23(3):427-40. 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 long-acting 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.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Animals
  • Anti-Obesity Agents / pharmacology*
  • Anti-Obesity Agents / therapeutic use
  • Antibodies, Monoclonal, Humanized / pharmacology*
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Blood Glucose
  • Body Weight / drug effects
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Evaluation, Preclinical
  • Female
  • Fibroblast Growth Factors / pharmacology*
  • Fibroblast Growth Factors / therapeutic use
  • Gene Expression / drug effects
  • Humans
  • Insulin / blood
  • Lipid Metabolism / drug effects
  • Macaca fascicularis
  • Male
  • Middle Aged
  • Obesity / blood
  • Obesity / drug therapy*
  • Subcutaneous Fat / drug effects
  • Subcutaneous Fat / metabolism
  • Weight Loss
  • Young Adult


  • Anti-Obesity Agents
  • Antibodies, Monoclonal, Humanized
  • Blood Glucose
  • Insulin
  • PF-05231023
  • Fibroblast Growth Factors