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

Abstract

The glucagon-like peptide-1 receptor (GLP-1R) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors have become important options for the management of patients with type 2 diabetes mellitus. While the GLP-1R agonists and DPP-4 inhibitors act on the incretin system to regulate glucose homeostasis, there are important clinical differences among the five agents currently available in the U.S. For example, the GLP-1R agonists require subcutaneous administration, produce pharmacological levels of GLP-1 activity, promote weight loss, have a more robust glucose-lowering effect, and have a higher incidence of adverse gastrointestinal effects. In contrast, the DPP-4 inhibitors are taken orally, increase the half-life of endogenous GLP-1, are weight neutral, and are more commonly associated with nasopharyngitis. Differences in efficacy, safety, tolerability, and cost among the incretin-based therapies are important to consider in the primary care management of patients with type 2 diabetes mellitus.

Figure 1

AACE/ACE diabetes algorithm for diabetes control. Algorithm for the metabolic management of type 2 diabetes. Lifestyle modification is a component of treatment for all patients. Interventions are stratified based upon the current A1C level and whether the patient is receiving treatment or is drug naïve. Medication choices are prioritized according to safety, risk of hypoglycemia, efficacy, simplicity, anticipated degree of patient adherence, and cost of medications. Only combinations of medications approved by the US Food and Drug Administration that provide complementary mechanisms of action are listed. It is essential to monitor therapy with A1C and self-monitoring of blood glucose and to adjust or advance therapy frequently (every 2 to 3 months) if the appropriate goal for each patient has not been achieved. [Reprinted from Endocrine Practice, Volume 15, Rodbard HW, Jellinger PS, Davidson JA, Einhorn D, Garber AJ, Grunberger G et al. Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control, Pages 540-559, Copyright 2009, with permission from the American Association of Clinical Endocrinologists.]

Figure 2

ADA/EASD algorithm for the management of patients with type 2 diabetes. Algorithm for the metabolic management of type 2 diabetes. Reinforce lifestyle interventions at every visit and check A1C every 3 months until A1C is < 7% and then at least every 6 months. The interventions should be changed if A1C is ≥ 7%. [Diabetes Care by American Diabetes Association. Copyright 2009 Reproduced with permission of American Diabetes Association in the format journal via Copyright Clearance Center]