Efficacy and safety of incretin-based therapies: Clinical trial data

Objective: Provide a comprehensive overview of efficacy and safety data on incretin-based agents in the treatment of type 2 diabetes. Data sources: A PubMed search was conducted for the years 2000-2009, using as keywords the names of glucagon-like peptide-1 (GLP-1) receptor agonists (exenatide and liraglutide) and dipeptidyl peptidase-4 (DPP-4) inhibitors (sitagliptin, alogliptin, and saxagliptin). World Diabetes Congress abstracts from 2008 to 2009 were also searched for clinical studies of these agents. Study selection: The author included randomized controlled trials of incretin therapies that were published in English and enrolled >= 100 participants. Data extraction: Data on the effects of incretins on glycemic control, weight, beta-cell function, blood pressure, lipid levels, safety, and tolerability were extracted and summarized. Data synthesis: A total of 27 randomized controlled studies of incretin therapy were identified and included in the review. GLP-1 receptor agonists and DPP-4 inhibitors were evaluated at different points in the diabetes treatment spectrum, i.e., added to diet and exercise alone (monotherapy) or added to oral antihyperglycemic regimens (combination therapy). Conclusion: In addition to decreasing glycemia in type 2 diabetes, incretin therapies may improve other important parameters, including beta-cell function, blood pressure, and lipid levels, with a low risk for hypoglycemia. A comparison of the study data differentiates the clinical profiles of the GLP-1 receptor agonists, which are associated with weight loss, and DPP-4 inhibitors, which are weight neutral, as well as the individual agents within each class.