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

Gregory Gaich, Jenny Y. Chien, Haoda Fu, Leonard C. Glass, Mark A. Deeg, William L. Holland, Alexei Kharitonenkov, Thomas Bumol, Holger K. Schilske, David E. Moller

Research output: Contribution to journalArticle

419 Citations (Scopus)

Abstract

Summary 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.

Original languageEnglish (US)
Pages (from-to)333-340
Number of pages8
JournalCell Metabolism
Volume18
Issue number3
DOIs
StatePublished - Sep 3 2013

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Type 2 Diabetes Mellitus
Placebos
Lipoprotein(a)
Apolipoproteins
Adiponectin
Dyslipidemias
LDL Cholesterol
HDL Cholesterol
Fasting
Therapeutics
Animal Models
Obesity
Body Weight
fibroblast growth factor 21
Insulin
Glucose

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

Cite this

Gaich, G., Chien, J. Y., Fu, H., Glass, L. C., Deeg, M. A., Holland, W. L., ... Moller, D. E. (2013). The effects of LY2405319, an FGF21 Analog, in obese human subjects with type 2 diabetes. Cell Metabolism, 18(3), 333-340. https://doi.org/10.1016/j.cmet.2013.08.005

The effects of LY2405319, an FGF21 Analog, in obese human subjects with type 2 diabetes. / 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.

In: Cell Metabolism, Vol. 18, No. 3, 03.09.2013, p. 333-340.

Research output: Contribution to journalArticle

Gaich, G, Chien, JY, Fu, H, Glass, LC, Deeg, MA, Holland, WL, Kharitonenkov, A, Bumol, T, Schilske, HK & Moller, DE 2013, 'The effects of LY2405319, an FGF21 Analog, in obese human subjects with type 2 diabetes', Cell Metabolism, vol. 18, no. 3, pp. 333-340. https://doi.org/10.1016/j.cmet.2013.08.005
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. / The effects of LY2405319, an FGF21 Analog, in obese human subjects with type 2 diabetes. In: Cell Metabolism. 2013 ; Vol. 18, No. 3. pp. 333-340.
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