Table of Contents
Pathophysiology of type 2 diabetes mellitus: potential role of incretin-based therapies
Glucose-lowering effects of incretin-based therapies
Safety, tolerability, and nonglycemic effects of incretin-based therapies
TAKE-HOME POINTS
- The “treat to target” approach is to quickly achieve the target glycosylated hemoglobin (AIC) goal of <7% in most people, and then intensify or change therapy as needed to maintain glycemic control
- Results of an online survey demonstrate uncertainty regarding the clinical differences between glucagon-like peptide (GLP-1) agonists and dipeptidyl peptidase (DPP)-4 inhibitors
- The increasingly important roles of the GLP-1 agonists and DPP-4 inhibitors stem from their overall good efficacy and safety profiles compared with other treatment options
The authors received editorial assistance from the Primary Care Education Consortium and WriteHealth, LLC in the development of this activity and honoraria from the Primary Care Education Consortium. They have disclosed that Dr Campbell is on the advisory board for Daiichi-Sankyo and the speakers bureau for Eli Lilly and Co; Dr Cobble is on the advisory board for Abbott Laboratories, AstraZeneca, and Eli Lilly and Co and speakers bureau for Abbott Laboratories, AstraZeneca/Bristol Myers Squibb, Eli Lilly and Co, GlaxoSmithKline, and Novo Nordisk Inc; Dr Reid is on the advisory board and speakers bureau for Amylin Pharmaceuticals, Medtronic, Novo Nordisk Inc, and sanofi-aventis; and Dr Shomali is on the advisory board for Novo Nordisk Inc and speakers bureau for Amylin Pharmaceuticals, Eli Lilly and Co, sanofi-aventis, and Takeda Pharmaceuticals.
The number of pharmacologic options available to treat type 2 diabetes mellitus (T2DM) has grown considerably over the past decade. With these options, health care providers have new opportunities to individualize treatment and provide better control of patients’ blood glucose levels. The “treat to failure” approach has been replaced by a “treat to target” approach, with the purpose of quickly achieving the A1C goal of <7.0% in most people, and then intensifying or changing therapy as needed to maintain glycemic control. At the same time, numerous questions have arisen, including where these new treatment options fit along the disease continuum, long-term safety, and how to treat T2DM from the time of diagnosis.
To better understand the questions and clinical challenges faced by primary care physicians, the Primary Care Education Consortium developed and distributed an online survey in February 2010 to primary care clinicians. The survey focused on the incretin class of glucose-lowering agents and was based on the results of reader surveys from 2 previous supplements of The Journal of Family Practice on incretin-based therapies, published in 2008 and 2009. The online survey was completed by 112 of the 1653 individuals (7% response) who received it.
The results of the online survey demonstrated a general understanding of the actions of incretin-based therapies—GLP-1 agonists and DPP-4 inhibitors—but uncertainty regarding their differences and roles in clinical management of patients with T2DM. These uncertainties are a concern because of the progressive nature of T2DM and the increasing importance of these agents in managing patients with T2DM, as reflected in guidelines and consensus statements issued in 2009 by the American Diabetes Association (ADA)/European Association for the Study of Diabetes1 and the American Association of Clinical Endocrinologists/American College of Endocrinology.2
The increasingly important roles of the GLP-1 agonists and DPP-4 inhibitors stem from their overall good efficacy and safety profiles compared with other treatment options, and from increasing experience not only from well-conducted clinical trials but also in clinical practice. Four incretin-based therapies are now available for use in the United States—exenatide and liraglutide, which are GLP-1 agonists, and sitagliptin and saxagliptin, which are DPP-4 inhibitors; liraglutide and saxagliptin were approved since publication of both guidelines in 2009. Although all are classified as incretin-based therapies, there are distinct differences between the GLP-1 agonists and DPP-4 inhibitors with respect to A1C reduction, effect on weight, and other nonglycemic parameters.
There are many issues with regard to providing comprehensive care to patients with T2DM that could be covered in this supplement. For example, as described in the ADA standards of care,3 the risks of other diseases, such as dyslipidemia, hypertension, and coronary heart disease, must also be considered in management of these patients. Glucose control remains a principal concern, however, and is the primary focus of this supplement.
Driven by results of the February 2010 online survey, this supplement builds upon the 2 previous supplements on incretin-based therapies to address 4 key areas:
- The pathophysiology of T2DM and the unique role of incretin hormones
- Glycemic control differences among available incretin-based agents
- Nonglycemic differences among available incretin-based agents
- Patient education regarding incretin-based therapies to promote patient self-management, with examples of patient cases for which incretin-based therapy is an option