Over the past several years, new drugs have emerged to expand our treatment armamentarium for type 2 diabetes, and these products have enhanced our understanding of the pathophysiology of type 2 diabetes. Newer therapies include the incretin class. The development of two products in the this class, glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, has demonstrated safe, effective, and beneficial effects that include lower fasting glucose and postprandial glucose, reduction of A1C, and lower risk for hypoglycemia.
How DPP-4 Inhibitors Work
DPP-4 is an enzyme that degrades endogenous GLP-1. While GLP-1 receptor agonists increase GLP-1 amounts and activity, DPP-4 inhibitors raise endogenous GLP-1 by inhibiting GLP-1 degradation. Levels of DPP-4 are increased by approximately six-fold. This results in increased insulin secretion, as well as a reduction of glucagon stimulation, which then results in improved fasting and postprandial glucose and improvements in A1C. There are currently just a couple of DPP-4 inhibitors available in the United States, but other agents are currently under FDA review. In clinical research, DPP-4 inhibitors have been well tolerated. An important consideration for patients who use these medications is that they are weight neutral and have been associated with a low risk of hypoglycemia. DPP-4 inhibitors are available for once-daily oral administration. This may improve adherence to drug regimens. They are also available in fixed-dosed combination with metformin, which may also be cost-effective and further improve patient adherence. The long-term safety of DPP-4 inhibitors is continuing to accumulate in medical research. Ongoing trials are addressing efficacy of this drug class as well as its role in cardiovascular disease safety. Clinicians should review contraindications and the full package insert of DPP-4 inhibitors prior to initiating these agents.
Implementing DPP-4 Inhibitors
Clinical guidelines are available to provide physicians with direction on when and how to use DPP-4 inhibitors. Guidelines support their use as monotherapy in treatment-naïve patients who have an initial A1C level in the lowest tertile, as well as in combination with metformin, sulfonylureas, and thiazolidinediones. DPP-4 inhibitors can be used in the spectrum of type 2 diabetes, but should also be considered for use early in the course of the disease because of functioning β-cells. As data continue to emerge, DPP-4 inhibitors will most likely augment the effects of existing therapies. This data should provide important clinical benefits for those who manage these patients.
Educating Patients on DPP-4 Inhibitors
To achieve long-term glycemic control, physicians must make efforts to educate patients about their diabetes with self-management strategies, including diet, exercise, and other lifestyle modifications. During patient education, physicians should address the use of different treatment options, including DPP-4 inhibitors, and inform patients about why they are taking them and how they work. When administering DPP-4 inhibitors, it is also crucial to discuss realistic expectations with patients. These medications, in conjunction with lifestyle modifications, have the potential to benefit patients and reduce the risk of diabetes-related complications. Involving other members of the diabetes management team may further help patients adhere to their medication and lifestyle regimens.
Readings & Resources (click to view)
Cobble ME, Freeman JS, Garber AJ, et al. The role of incretin therapy for type 2 diabetes in family medicine. J Fam Prac. 2008;57(Suppl 1):S2-S31. Available at:http://www.jfponline.com/ccp_article.asp?id=6684.
Garber AJ. Incretin-based therapies in the management of type 2 diabetes: rationale and reality in a managed care setting. Am J Manag Care. 2010;16(Suppl):S187-S194. Available at:http://www.ajmc.com/supplement/managed-care/2010/A292_10aug/A292_10aug_Garber_S187to194.
Gerich J. DPP-4 inhibitors: what may be the clinical differentiators? Diabetes Res Clin Pract. 2010;90:131-140. Available at: http://www.diabetesresearchclinicalpractice.com/article/S0168-8227(10)00361-X/abstract.
Campbell RK, Cobble ME, Teid TS, Shomali ME. Distinguishing among incretin-based therapies. Pathophysiology of type 2 diabetes mellitus: potential role of incretin-based therapies. J Fam Prac. 2010;59 (Suppl 1): S5-S9. Available at: http://www.jfponline.com/Pages.asp?AID=8943.