Abstract

Glucose homeostasis is regulated by a complex interplay of multiple hormones, including hormones from the pancreas (insulin, glucagon, and amylin) and the gut (glucagon-like peptide 1 [GLP-1] and glucose-dependent insulinotropic polypeptide). Most therapeutic options are focused on abnormal insulin secretion and signalling and do not address the role these other hormones play in glucoregulation and the diabetic state.

The inability to control glycemia over the long term utilizing single oral agents is reflected by the need to use various agents, alone or in combination, over time. In addition, the presence of associated side effects and clinical shortcomings of many therapies has prompted the search for new therapeutic agents that address the underlying dysregulation of multiple hormones found in people with diabetes. One of these agents, exenatide, mimics several of the actions of GLP-1 and is the first agent in a new class called incretin mimetics.

Exenatide was approved by the Food and Drug Administration in 2005 as an adjunctive therapy to metformin and/or sulfonylurea regimens for individuals with type 2 diabetes who have not achieved adequate glycemic control. Clinical trials indicate that subjects taking 10 μg of exenatide twice daily for 6 months had hemoglobin A_1c (A1C) reductions of ∼1% and body weight reductions of ∼2 kg. After 1.5 years of exenatide treatment, reductions in A1C were sustained (1.1%), and body weight reductions were progressive (4.4 kg). In addition, exenatide treatment for 1.5 years resulted in improvements in some cardiovascular risk factors. For individuals with type 2 diabetes not achieving adequate glucose control with metformin and/or sulfonylureas, incretin mimetics such as exenatide may offer the opportunity for improved glycemic control with fewer clinical shortcomings than other available treatments.