title: A Long-Acting FGF21 Molecule, PF-05231023, Decreases Body Weight and Improves Lipid Profile in Non-human Primates and Type 2 Diabetic Subjects.
abstract: 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.
authors.affiliation: Cardiovascular Metabolic and Endocrine Disease Research Unit, Pfizer Worldwide Research and Development, 610 Main Street, Cambridge, MA 02139, USA. Electronic address: mumpi462@yahoo.com.
authors.forename: Saswata
authors.initials: S
authors.lastname: Talukdar
authors.affiliation: Cardiovascular Metabolic and Endocrine Disease Research Unit, Pfizer Worldwide Research and Development, 610 Main Street, Cambridge, MA 02139, USA.
authors.forename: Yingjiang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Cardiovascular Metabolic and Endocrine Disease Research Unit, Pfizer Worldwide Research and Development, 610 Main Street, Cambridge, MA 02139, USA.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Li
authors.affiliation: Cardiovascular Metabolic and Endocrine Disease Research Unit, Pfizer Worldwide Research and Development, 610 Main Street, Cambridge, MA 02139, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Rossulek
authors.affiliation: Cardiovascular Metabolic and Endocrine Disease Research Unit, Pfizer Worldwide Research and Development, 610 Main Street, Cambridge, MA 02139, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Dong
authors.affiliation: Cardiovascular Metabolic and Endocrine Disease Research Unit, Pfizer Worldwide Research and Development, 610 Main Street, Cambridge, MA 02139, USA.
authors.forename: Veena
authors.initials: V
authors.lastname: Somayaji
authors.affiliation: Pharmacokinetics, Dynamics, and Metabolism, Pfizer Worldwide Research and Development, 610 Main Street, Cambridge, MA 02139, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Weng
authors.affiliation: Cardiovascular Metabolic and Endocrine Disease Research Unit, Pfizer Worldwide Research and Development, 610 Main Street, Cambridge, MA 02139, USA.
authors.forename: Ronald
authors.initials: R
authors.lastname: Clark
authors.affiliation: Cardiovascular Metabolic and Endocrine Disease Research Unit, Pfizer Worldwide Research and Development, 610 Main Street, Cambridge, MA 02139, USA.
authors.forename: Adhiraj
authors.initials: A
authors.lastname: Lanba
authors.affiliation: Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Bryn M
authors.initials: BM
authors.lastname: Owen
authors.affiliation: Cardiovascular Metabolic and Endocrine Disease Research Unit, Pfizer Worldwide Research and Development, 610 Main Street, Cambridge, MA 02139, USA.
authors.forename: Martin B
authors.initials: MB
authors.lastname: Brenner
authors.affiliation: Cardiovascular Metabolic and Endocrine Disease Research Unit, Pfizer Worldwide Research and Development, 610 Main Street, Cambridge, MA 02139, USA.
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Trimmer
authors.affiliation: Drug Safety Research and Development, Pfizer Inc., Groton, CT 06340, USA.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Gropp
authors.affiliation: Pharmacokinetics, Dynamics, and Metabolism, Pfizer Worldwide Research and Development, 610 Main Street, Cambridge, MA 02139, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Chabot
authors.affiliation: Cardiovascular Metabolic and Endocrine Disease Research Unit, Pfizer Worldwide Research and Development, 610 Main Street, Cambridge, MA 02139, USA.
authors.forename: Derek M
authors.initials: DM
authors.lastname: Erion
authors.affiliation: Cardiovascular Metabolic and Endocrine Disease Research Unit, Pfizer Worldwide Research and Development, 610 Main Street, Cambridge, MA 02139, USA.
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Rolph
authors.affiliation: Cardiovascular Metabolic and Endocrine Disease Research Unit, Pfizer Worldwide Research and Development, 610 Main Street, Cambridge, MA 02139, USA.
authors.forename: Bryan
authors.initials: B
authors.lastname: Goodwin
authors.affiliation: Cardiovascular Metabolic and Endocrine Disease Research Unit, Pfizer Worldwide Research and Development, 610 Main Street, Cambridge, MA 02139, USA. Electronic address: roberto.a.calle@pfizer.com.
authors.forename: Roberto A
authors.initials: RA
authors.lastname: Calle
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology* / Q000627:therapeutic use; D001786:Blood Glucose; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004353:Drug Evaluation, Preclinical; D005260:Female; D005346:Fibroblast Growth Factors / Q000494:pharmacology* / Q000627:therapeutic use; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000097:blood; D050356:Lipid Metabolism / Q000187:drug effects; D008252:Macaca fascicularis; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000188:drug therapy*; D050151:Subcutaneous Fat / Q000187:drug effects / Q000378:metabolism; D015431:Weight Loss; D055815:Young Adult
chemical_list: D019440:Anti-Obesity Agents; D061067:Antibodies, Monoclonal, Humanized; D001786:Blood Glucose; D007328:Insulin; C000604284:PF-05231023; D005346:Fibroblast Growth Factors