• Cassie L Boland, Michelle Degeeter, Donald S Nuzum, and Maria Tzefos.
• School of Pharmacy, Wingate University, Wingate, NC, USA. c.boland@wingate.edu
• Ann Pharmacother. 2013 Apr 1; 47 (4): 490-505.

ObjectiveTo discuss the controversy surrounding selection of second-line type 2 diabetes mellitus (T2DM) therapy by reviewing available data regarding secondary effects of glucagon-like peptide-1 receptor (GLP-1) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, which include low hypoglycemia risk, weight loss, and cardiovascular (CV) and β-cell function benefits.Data SourcesA MEDLINE search (1966-March 2013) was conducted using the following key terms: β-cell protection, blood pressure, DPP-4 inhibitors, exena tide, exenatide extended-release, GLP-1 agonists, hypoglycemia, lina glip tin, lipid, liraglutide, pancreatitis, saxagliptin, sitagliptin, and type 2 diabetes.Study Selection And Data ExtractionIdentified articles published in English were evaluated for inclusion, with priority given to randomized controlled trials in humans receiving incretin monotherapy or incretin combination therapy with metformin. References identified in these articles were reviewed for additional trials.Data SynthesisMost patients with T2DM use combination therapy; however, determination of the second-line agent that is most appropriate is debatable. Prior to the use of incretin therapies, traditional second-line agents included sulfonylureas, thiazolidinediones, and basal insulin, all of which demonstrate undesirable adverse effects. In addition to improving glycemic control, incretin therapies have demonstrated benefits concerning hypoglycemic risk and weight loss in addition to potential improvements in CV risk factors and β-cell function. While there are risks associated with using incretins, most patients with T2DM are good candidates for incretins and could benefit from their potential secondary effects. Cost remains a barrier to initiating these agents.ConclusionsDemonstrated secondary benefits in addition to efficacy may make GLP-1 agonists and DPP-4 inhibitors a more favorable option than other second-line T2DM therapies.

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