The improved understanding of glucoregulatory
hormones has driven the development of new pharmacologic agents to treat
type 2 diabetes. One new class of
antihyperglycemic medication is
incretin mimetics (IMs).
Incretin hormones potentiate insulin secretion following meal ingestion, a process that is impaired in patients with
type 2 diabetes.
GLP-1, a 30-amino
acid peptide incretin hormone, is produced in the L cells of the ileum and colon. Studies have shown that a 6-week continuous
GLP-1 infusion in patients with
type 2 diabetes improved
glycemic control and beta-cell function and delayed gastric emptying. Despite the rapid degradation and inactivation of
GLP-1 by the
enzyme dipeptidyl peptidase IV (DPP-IV), agents that mimic the actions of
GLP-1 are of great clinical interest. First-in-class IM
exenatide, a
GLP-1 receptor agonist resistant to DPP-IV inactivation, mimics many beneficial glucoregulatory effects of
GLP-1, such as suppressing
glucagon secretion, regulating gastric emptying and satiety, and increasing
glucose-dependent insulin secretion.
Exenatide is an adjunctive
therapy for patients who take
metformin, a sulfonylurea, a
thiazolidinedione, or a combination of these oral medications but have not achieved
glycemic control. An 82-week, open-label extension trial has shown that
exenatide is well tolerated and that the benefits, including improved
glycemic control,
weight loss, and mitigation of cardiovascular risk factors, are sustained.