title: The effects of LY2405319, an FGF21 analog, in obese human subjects with type 2 diabetes.
abstract: Fibroblast growth factor 21 (FGF21) is a recently discovered metabolic regulator. Exogenous FGF21 produces beneficial metabolic effects in animal models; however, the translation of these observations to humans has not been tested. Here, we studied the effects of LY2405319 (LY), a variant of FGF21, in a randomized, placebo-controlled, double-blind proof-of-concept trial in patients with obesity and type 2 diabetes. Patients received placebo or 3, 10, or 20 mg of LY daily for 28 days. LY treatment produced significant improvements in dyslipidemia, including decreases in low-density lipoprotein cholesterol and triglycerides and increases in high-density lipoprotein cholesterol and a shift to a potentially less atherogenic apolipoprotein concentration profile. Favorable effects on body weight, fasting insulin, and adiponectin were also detected. However, only a trend toward glucose lowering was observed. These results indicate that FGF21 is bioactive in humans and suggest that FGF21-based therapies may be effective for the treatment of selected metabolic disorders.
authors.affiliation: Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Gaich
authors.forename: Jenny Y
authors.initials: JY
authors.lastname: Chien
authors.forename: Haoda
authors.initials: H
authors.lastname: Fu
authors.forename: Leonard C
authors.initials: LC
authors.lastname: Glass
authors.forename: Mark A
authors.initials: MA
authors.lastname: Deeg
authors.forename: William L
authors.initials: WL
authors.lastname: Holland
authors.forename: Alexei
authors.initials: A
authors.lastname: Kharitonenkov
authors.forename: Thomas
authors.initials: T
authors.lastname: Bumol
authors.forename: Holger K
authors.initials: HK
authors.lastname: Schilske
authors.forename: David E
authors.initials: DE
authors.lastname: Moller
mesh_terms: D052242:Adiponectin / Q000097:blood; D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D001835:Body Weight; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D050171:Dyslipidemias / Q000150:complications / Q000188:drug therapy; D005260:Female; D005346:Fibroblast Growth Factors / Q000627:therapeutic use*; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000188:drug therapy*; D015990:Placebo Effect; D014280:Triglycerides / Q000097:blood; D055815:Young Adult
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D007328:Insulin; C585266:LY2405319; D014280:Triglycerides; D005346:Fibroblast Growth Factors