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Fibroblast Growth Factor-Based Pharmacotherapies for the Treatment of Obesity-Related Metabolic Complications

Leigang Jin1,2, Ranyao Yang1,2, Leiluo Geng1,2

  • 1State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China.

Annual Review of Pharmacology and Toxicology
|September 13, 2022
PubMed

Insights

Fibroblast growth factor (FGF) therapies show promise for metabolic disorders like NASH. While effective for liver conditions, their impact on diabetes and obesity varies, requiring further research for optimal clinical use.

Area of Science:

  • Metabolic research
  • Endocrinology
  • Biopharmaceutical development

Background:

  • The fibroblast growth factor (FGF) family includes 22 proteins regulating cell functions.
  • Specific FGF members (FGF1, FGF4, FGF19, FGF21) are key in energy homeostasis, metabolism, and insulin sensitivity.
  • Preclinical data support FGF therapeutic potential for obesity, diabetes, dyslipidemia, and NASH.

Purpose of the Study:

  • To review advancements in FGF-based biopharmaceuticals for metabolic complications.
  • To identify challenges in clinical application of FGF therapies.
  • To propose strategies for overcoming clinical implementation hurdles.

Main Methods:

  • Review of preclinical and clinical trial data on FGF analogs.
  • Analysis of pharmacodynamic and pharmacokinetic properties of engineered FGFs.
  • Evaluation of therapeutic efficacy in obesity-related metabolic diseases.

Main Results:

  • Engineered FGF19 and FGF21 analogs are in clinical trials.
  • FGF analogs effectively treat hepatic steatosis, steatohepatitis, and fibrosis in NASH patients.
  • Antidiabetic and antiobesity effects of FGF analogs are modest and inconsistent across trials.

Conclusions:

  • FGF-based therapies show significant potential for NASH treatment.
  • Clinical efficacy for diabetes and obesity requires further optimization.
  • Addressing challenges in clinical implementation is crucial for broader therapeutic success.
Keywords:
agonistic antibodiesfibroblast growth factorsmetabolic complicationsobesityprotein therapeutics

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