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

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 (HbA(1c)) 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. (C) 2015 Elsevier HS Journals, Inc. All rights reserved.