The effects of LY2405319, an FGF21 analog, in obese human subjects with type 2 diabetes

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,...

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Vydáno v:Cell metabolism Ročník 18; číslo 3; s. 333
Hlavní autoři: Gaich, Gregory, Chien, Jenny Y, Fu, Haoda, Glass, Leonard C, Deeg, Mark A, Holland, William L, Kharitonenkov, Alexei, Bumol, Thomas, Schilske, Holger K, Moller, David E
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 03.09.2013
Témata:
Adiponectin - blood
Adolescent
Adult
Aged
Blood Glucose - analysis
Body Mass Index
Body Weight
Cholesterol, HDL - blood
Cholesterol, LDL - blood
Diabetes Mellitus, Type 2 - complications
Diabetes Mellitus, Type 2 - drug therapy
Double-Blind Method
Dyslipidemias - complications
Dyslipidemias - drug therapy
Female
Fibroblast Growth Factors - therapeutic use
Humans
Insulin - blood
Male
Middle Aged
Obesity - complications
Obesity - drug therapy
Placebo Effect
Triglycerides - blood
Young Adult
ISSN:1932-7420, 1932-7420
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Shrnutí: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.
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ISSN:1932-7420
1932-7420
DOI:10.1016/j.cmet.2013.08.005