Incretin-Based Therapies for Type 2 Diabetes Mellitus: Current Status and Future Prospects
Article first published online: 6 JAN 2012
2010 Pharmacotherapy Publications Inc.
Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy
Volume 30, Issue 6, pages 609–624, June 2010
How to Cite
Drab, S. R. (2010), Incretin-Based Therapies for Type 2 Diabetes Mellitus: Current Status and Future Prospects. Pharmacotherapy, 30: 609–624. doi: 10.1592/phco.30.6.609
- Issue published online: 6 JAN 2012
- Article first published online: 6 JAN 2012
- type 2 diabetes;
- incretin-based therapies;
- glucagon-like peptide-1;
- dipeptidyl peptidase-4;
Incretin-based therapies encompass two new classes of antidiabetic drugs: glucagon-like peptide-1 (GLP-l) receptor agonists (e.g., liraglutide, exenatide, and exenatide long-acting release), which are structurally related to GLP-l, and the dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g., sitagliptin and saxagliptin), which limit the breakdown of endogenous GLP-l. 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 A1c levels, with very low rates of hypoglycemia. In addition, reductions in body weight have been observed with GLP-l receptor agonists, which also exert a pronounced effect on systolic blood pressure. Various human and animal studies show that GLP-l improves β-cell function and increases β-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.