Battle of GLP-1 delivery technologies

Adv Drug Deliv Rev. 2018 May;130:113-130. doi: 10.1016/j.addr.2018.07.009. Epub 2018 Jul 21.


Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) belong to an important therapeutic class for treatment of type 2 diabetes. Six GLP-1 RAs, each utilizing a unique drug delivery strategy, are now approved by the Food and Drug Administration (FDA) and additional, novel GLP-1 RAs are still under development, making for a crowded marketplace and fierce competition among the manufacturers of these products. As rapid elimination is a major challenge for clinical application of GLP-1 RAs, various half-life extension strategies have been successfully employed including sequential modification, attachment of fatty-acid to peptide, fusion with human serum albumin, fusion with the fragment crystallizable (Fc) region of a monoclonal antibody, sustained drug delivery systems, and PEGylation. In this review, we discuss the scientific rationale of the various half-life extension strategies used for GLP-1 RA development. By analyzing and comparing different approved GLP-1 RAs and those in development, we focus on assessing how half-life extending strategies impact the pharmacokinetics, pharmacodynamics, safety, patient usability and ultimately, the commercial success of GLP-1 RA products. We also anticipate future GLP-1 RA development trends. Since similar drug delivery strategies are also applied for developing other therapeutic peptides, we expect this case study of GLP-1 RAs will provide generalizable concepts for the rational design of therapeutic peptides products with extended duration of action.

Keywords: Albumin fusion; Exenatide; Fatty acid conjugate; Fc fusion; GLP-1 receptor agonist; Half-life; Peptide delivery; Pharmacokinetics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Drug Delivery Systems*
  • Glucagon-Like Peptide 1 / pharmacology*
  • Glucagon-Like Peptide-1 Receptor / agonists*
  • Glucagon-Like Peptide-1 Receptor / metabolism
  • Humans
  • Hypoglycemic Agents / pharmacology*


  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Glucagon-Like Peptide 1