Details

Autor(en) / Beteiligte

• 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.

Titel

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

Ist Teil von

• Cell metabolism, 2016-03, Vol.23 (3), p.427-440

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •The FGF21 analog PF-05231023 reduced body weight in obese monkeys and humans•PF-05231023 improved the circulating lipid profile in monkeys and humans•PF-05231023 elevated adiponectin levels but did not improve glycemic control•Multiple markers of bone formation and resorption were modulated by PF-05231023 Talukdar et al. describe the effects of a long-acting FGF21 analog, PF-05231023, in obese monkeys and obese/overweight humans with type 2 diabetes. In both humans and monkeys, PF-05231023 decreased body weight, improved the circulating lipid profile and increased adiponectin levels. In humans, PF-05231023 treatment resulted in multiple changes in markers of bone turnover.