Emerging New Therapies for the Treatment of Type 2 Diabetes Mellitus: Glucagon-like Peptide-1 Receptor Agonists

• Published in: Clinical therapeutics 2015-03, Vol.37 (3), p.483-493
• Main Authors: Lindamood, Christopher A, Taylor, James R., PharmD, CDE
• Format: Article
• Language: English
• Subjects: Adult; albiglutide; Clinical trials; Clinical Trials, Phase III as Topic; Diabetes; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Drug Administration Schedule; dulaglutide; exenatide; GLP-1 receptor agonists; Glucagon-Like Peptide 1 - analogs & derivatives; Glucagon-Like Peptide 1 - therapeutic use; Glucagon-Like Peptide-1 Receptor - therapeutic use; Glucagon-Like Peptides - analogs & derivatives; Glucagon-Like Peptides - therapeutic use; Glucose; Glycated Hemoglobin A - analysis; Humans; Hypoglycemia - drug therapy; Hypoglycemic Agents - therapeutic use; Immunoglobulin Fc Fragments - therapeutic use; Insulin; Insulin resistance; Internal Medicine; liraglutide; Liraglutide - therapeutic use; lixisenatide; Medical Education; Middle Aged; Pathogenesis; Peptides; Peptides - therapeutic use; Randomized Controlled Trials as Topic; Receptors, Glucagon - agonists; Recombinant Fusion Proteins - therapeutic use; Studies; Venoms - therapeutic use
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/j.clinthera.2015.01.003

Abstract Purpose The goal of this article was to review the safety, efficacy, and potential for utilization of the newly approved once-weekly glucagon-like peptide-1 (GLP-1) receptor agonists in the treatment of type 2 diabetes. Methods Published articles for Phase III trials were found by performing a MEDLINE search using the search terms exenatide , exenatide once weekly , DURATION, albiglutide , and HARMONY as key terms. Search results were restricted by using filters to include clinical trials in humans. A search of relevant diabetes journals (including Diabetes Care and Diabetologia ) was also performed to find abstracts for studies that did not have complete published articles at the time of this review. Findings Exenatide once weekly reduced glycosylated hemoglobin (HbA1c ) by –1.0% to –2.0% when used as monotherapy and add-on therapy; it also provided significant weight loss ranging from 2 to 4 kg and maintained a relatively low risk of hypoglycemia. Albiglutide was able to reduce glycosylated hemoglobin levels between –0.5% and –0.84% when used as monotherapy and in combination with other antidiabetic medications. The newest once-weekly GLP-1 receptor agonist, dulaglutide, reduced glycosylated hemoglobin levels between –0.78% and –1.51% and demonstrated noninferiority to once-daily liraglutide. Implications The GLP-1 receptor agonists have proven efficacy in the treatment of type 2 diabetes and may provide patients with additional nonglycemic benefits, including significant weight loss and decreased systolic blood pressure. The newer once-weekly formulations are more convenient than the BID and once-daily medications, which could improve adherence and may be more attractive to providers and patients.