Preclinical Research

Mimetics of Glucagon‐like peptide 1 (GLP‐1) represent a useful alternative or complementary treatment choice to insulin in the treatment of diabetes mellitus. The lack of hypoglycemia as a side effect when GLP‐1 receptor agonists are used along with the tendency of these therapeutic agents to prevent or even reduce weight gain makes them valuable targets in therapy development. However, native GLP‐1 and many of its early analogues have very short half‐lives, requiring repeated treatment to maintain therapeutic levels. As all current treatments are injected subcutaneously, a large focus has been made on trying to extend the half‐lives of GLP‐1 analogues while retaining bioactivity. Most success in this regard has been achieved with the use of peptide‐protein fusions, which are not as well suited for oral administration. However, recent work focused on the development of non‐fusion peptides with increased half‐lives that may be more appropriate for oral administration. This minireview discusses the structural characteristics of past and present analogues as well as the recent work conducted toward developing novel GLP‐1 receptor agonists. Drug Dev Res 78 : 292–299, 2017. © 2017 Wiley Periodicals, Inc.