Glucagon-Like Peptide-1 Receptor Agonists
The newest class of antidiabeteic medications to be approved for use in the United States is the glucagon-like- peptide-1 agonists (GLP-1). There are two drugs in this class that are currently available, exenatide (Byetta, Bydurian) and liraglutide (Victoza) (LexiComp, 2014). These medications mimic the actions of endogenous GLP-1. Endogenous GLP-1 is secreted from the L-cells in the colon and ileum in response to the ingestion of nutrients (Ryan, Foster, & Jobe, 2011, p. 794). GLP-1 has a half-life of 2 minutes due to the action of the DPP-4 enzymes. GLP-1 agonists overcome this issue by having an altered structure that renders them less susceptible to DPP-4 enzymatic degradation thus prolonging the effects of GLP-1 (ADA, 2014, p. 621).
The first glucagon-like peptide 1 agonist to be developed was exenatide. Exenatide was approved for use in the United States in 2005. It is a synthetic form of a molecule exendin-4. Interestingly, this compound was discovered in the saliva of the Gila monster, a reptile found in the desert southwest of North America. This compound was found to be 53% identical to human GLP-1 and mimics GLP-1 on human receptors with a greater stability than native human GLP-1 hormone. (Furman, 2012, p. 464)
In January of 2010, the Food and Drug Administration approved liraglutide for use in the treatment of type 2 diabetes in the United States. Liraglutide is a synthetic form of the human GLP-1 hormone that has been altered in its molecular structure. The alterations increase aggregation of the drug, decreases the binding to albumin, and is more resistant to degradation by DPP-4 enzymes (Ryan et al., 2011, p. 795). These properties increase the bioavailability of the drug and augment the effects. Half-life of this drug is eleven to fifteen hours, making daily dosing possible as opposed to exenatide that is dosed twice daily. However, long acting exenatide has been approved and allows for weekly dosing and marketed under the name Bydurion (exenatide LAR). (Tierney, 2012, p. 241)
Current guidelines from the American Diabetic Association recommend the use of GLP-1 agonists as second-line therapy in addition to the use of metformin. However, recommendations from the American Association of Clinical Endocrinologists and the American College of Endocrinologists support the use of GLP-1 agonists as first-line monotherapy in patients whose HbA1c is between 6.5% and 7.5% and recommend the addition of metformin in patients whose HbA1c are between 7.6% and 8.5% (Garber et al., 2013, p. 4).
Metformin is the preferred treatment for type 2 diabetes based on the guidelines established by the American Diabetic Association (ADA, 2014, p. S20). The ADA recognizes that type 2 diabetes is a progressive disease that may require the addition of other pharmacological agents in addition to continued lifestyle modification to control hyperglycemia and to...