The Battle of Delivery Strategies for GPL-1 Peptide
Ekaterina I. Shishatskaya
Steven P. Schwendeman
Институт фундаментальной биологии и биотехнологии
Кафедра медицинской биологии
Journal Name:Advanced Drug Delivery Reviews
Journal Quartile in Scopus:Q1
Journal Quartile in Web of Science:Q1
Bibliographic Citation:Minzhi, Yu. The Battle of Delivery Strategies for GPL-1 Peptide [Текст] / Yu Minzhi, Mason Benjamin, Srinivasan Santhanakrishnan, Ekaterina I. Shishatskaya, Steven P. Schwendeman, Schwendeman Anna // Advanced Drug Delivery Reviews. — 2018.
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.