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.