Incretin-Based Therapies for Type 2 Diabetes Mellitus: Current Status and Future Prospects

Incretin-based therapies encompass two new classes of antidiabetic drugs: glucagon-like peptide-1 (GLP-1) receptor agonists (e.g., liraglutide, exenatide, and exenatide long-acting release), which are structurally related to GLP-1, and the dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g., sitagliptin and saxagliptin), which limit the breakdown of endogenous GLP-1. To evaluate the safety and effectiveness of incretin-based therapies for the treatment of type 2 diabetes mellitus and the role of these therapies in clinical practice, a MEDLINE search (January 1985 November 2009) was conducted. Relevant references from the publications identified were also reviewed. Of 28 studies identified, 22 were randomized controlled trials. Data show that these therapies affect insulin secretion in a glucose-dependent manner, achieving clinically meaningful reductions in hemoglobin A(1c) levels, with very low rates of hypoglycemia. In addition, reductions in body weight have been observed with GLP-1 receptor agonists, which also exert a pronounced effect on systolic blood pressure. Various human and animal studies show that GLP-1 improves beta-cell function and increases beta-cell proliferation in vitro, which may slow disease progression. Thus, incretin-based therapies represent a promising addition to the available treatments for type 2 diabetes.