Differentiating among incretin-based therapies in the management of patients with type 2 diabetes mellitus

Treating patients with type 2 diabetes mellitus (T2DM) can be very challenging. Fortunately, new treatment options for T2DM, such as incretin-based agents, provide new opportunities to bring the disease under control, and perhaps slow its progression. More recently, focus has been placed on 'treating to target' glucose approaches rather than waiting for progressive glucose failure. The goal of the treat-to-target approach is to achieve safe glucose targets for each individual with a combination of early lifestyle and pharmacologic therapies. As such, it is important to work with each patient to develop and initiate a lifestyle and pharmacologic treatment plan at the time of diagnosis of T2DM to achieve the glycemic target--generally an A1C < 7.0% [1], within 3 to 6 months. The second and very important part of the treat-to-target approach is to modify treatment as needed to maintain the A1C at the target level [2]. Modifying treatment is, however, often challenging because of hypoglycemia, weight gain, intolerable adverse events, even access to and affordability of newer agents, as well as clinical inertia. These and other glycemic and non-glycemic factors were considered by the American Diabetes Association/European Society for the Study of Diabetes (ADA/EASD) [2] and by the American Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE) [3] when developing their 2009 guideline recommendations. Both groups concluded that, based upon their unique physiologic activity, efficacy, nonglycemic benefits, and safety profiles, agents which act on the incretin system--the glucagon-like peptide-1 (GLP-1R) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors--are important options for the management of patients with T2DM. An agent in each class has now been FDA-approved since 2005 and 2006. (Table 1)The AACE/ACE guidelines, for example, state that the GLP-1R agonists and DPP-4 inhibitors are options as monotherapy for patients with an A1C of 6