Exendin-4, a 39-amino-acid peptide found in lizard saliva, is a glucagon-like
peptide-1 (GLP-1) receptor agonist that has been approved for the treatment of type 2
diabetes by the United States Food and Drug Administration (FDA) since 2005. More
recently, exendin-4–loaded extended-release microspheres, the first once-weekly
treatment for type 2 diabetes, were also approved by the FDA in 2012. Exendin-4
exerts many beneficial anti-diabetes bioactivities, including induction of glucosedependent
insulin secretion, suppression of high glucagon secretion, slowing of gastric
emptying to modulate nutrient absorption, reduction of food intake and body weight,
improvement in pancreatic endocrine function, and an increase in β-cell mass. In this
chapter, the historical perspective, present status and related mechanisms of exendin-4
for the treatment of type 2 diabetes are discussed. Moreover, strategies that have been
applied for the design of exendin-4 derivatives and their potential applications are
summarized and discussed. This chapter will benefit future prospects of the use of
exendin-4 and its derivatives in the treatment of type 2 diabetes and obesity.
Keywords: Bile acid, Bioavailability, Blood glucose, Chitosan, Conjugation,
Delivery system, Dimerization, Exendin-4, Fatty acid, Fusion protein, GLP-1
receptor, Human serum albumin, Modification, PEGylation, Vitamin.
