Clinical efficacy of GLP-1 agonists and their place in the diabetes treatment algorithm

Incretin-based therapies (subcutaneously administered glucagon-like peptide-1 [GLP-1] agonists and oral dipeptidyl peptidase-4 inhibitors) represent a new mechanism of action with which to target the adverse effects of type 2 diabetes mellitus. Both classes of incretins are excellent choices for patients who have jobs that do not permit use of insulin therapy, who have hypoglycemic unawareness, or for whom hypoglycemia is an especially worrisome potential adverse effect. Glucagon-like peptide-1 agonists are an attractive choice for patients in whom promotion of weight loss is a major consideration and the glycated hemoglobin level is moderately elevated (<8.0%) (ie, insulin is not required). Short-acting exenatide has been available since 2005 and is administered twice a day before meals. Liraglutide is the first of the long-acting GLP-1 agonists to be approved in the United States and is administered once a day. The most common adverse effects of GLP-1 agonists are those related to the gastrointestinal system. Both exenatide and liraglutide are associated with weight loss when used as monotherapy or as part of combination-therapy strategies. Glucagon-like peptide-1 agonists also have beneficial effects on cardiovascular risk factors such as blood pressure and lipids.