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Sustained release of a GLP-1 and FGF21 dual agonist from an injectable depot protects mice from obesity and

C A Gilroy1,2, M E Capozzi3, A K Varanko1

  • 1Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA.

Science Advances
|September 14, 2020
PubMed

Insights

A novel dual-agonist combining glucagon-like peptide-1 (GLP-1) and fibroblast growth factor 21 (FGF21) effectively promotes weight loss and improves glycemic control in diabetic mice. This combination therapy shows superior results compared to individual treatments.

Area of Science:

  • Metabolic disease research
  • Pharmacology and drug development
  • Biotechnology

Background:

  • Type 2 diabetes management seeks effective weight loss therapies.
  • Glucagon-like peptide-1 (GLP-1) agonists are used for diabetes and weight management.
  • Fibroblast growth factor 21 (FGF21) exhibits thermogenic and insulin-sensitizing properties.

Purpose of the Study:

  • To develop and evaluate a novel dual-agonist biologic combining GLP-1 and FGF21.
  • To assess the efficacy of this dual-agonist for weight loss and glycemic control in type 2 diabetes.
  • To investigate the benefits of a sustained-release formulation for combination therapy.

Main Methods:

  • Development of a fusion biologic linking GLP-1 and FGF21 using an elastin-like polypeptide linker for sustained release.
  • Administration of the dual-agonist therapy once weekly to diabetic mice.
  • Comparison of the dual-agonist's efficacy against individual agonists and a simple mixture.

Main Results:

  • Once-weekly dual-agonist treatment resulted in significant weight reduction in diabetic mice.
  • Enhanced glycemic control was observed with the dual-agonist therapy.
  • The dual-agonist formulation demonstrated superior efficacy compared to individual GLP-1 or FGF21 treatments and a mixture.

Conclusions:

  • A GLP-1/FGF21 dual-agonist with sustained release is a promising therapeutic strategy for type 2 diabetes.
  • Combining GLP-1 and FGF21 into a single molecule offers enhanced efficacy for metabolic disease treatment.
  • Further research into GLP-1/FGF21 multiagonism is warranted for metabolic disease management.

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