Incretin Therapies in Diabetes Care

Diabetes is an epidemic in the United States. According to the most recent CDC estimates, the disease affects approximately 25.8 million Americans, representing 8.3% of the total population. Over the course of several years, safer and more effective therapies and treatment options have emerged to improve patient management. A greater understanding of the pathogenesis of diabetes has led to the development of additional therapies to individualize treatment approaches. Examining the Incretin System Type 2 diabetes is a progressive disease that results from a complex process that includes declining b-cell function and insulin resistance. Other factors that play a role include unsuppressed glucagon and impaired incretin function. The role of the incretin system in diabetes has been studied for several decades, and therapeutic agents that target these hormones have become available. These incretin hormones are synthesized predominantly in the small bowel. The major incretins in humans are GLP-1 (glucagon-like polypeptide) and GIP (glucose-dependent insulinotropic polypeptide). These hormones can increase insulin secretion, reduce glucagon secretion, slow gastric emptying, and enhance early satiety, all of which may ultimately improve glucose homeostasis. “The glucose-lowering effects of incretin-based therapies can provide the most beneficial improvements if they’re used early in the course of treatment.” Native GLP-1 has a short half-life of approximately 3 minutes and is degraded by the dipeptidyl peptidase-4 (DPP-4) enzyme. Synthetic GLP-1 agonists are not degraded by this enzyme and provide pharmacologic levels of GLP. By achieving these levels of GLP-1, delayed gastric emptying and early satiety occurs. DPP-4 inhibitors delay the breakdown of endogenous GLP-1, and therefore provide levels of GLP-1 slightly higher than normal. Both of these agents lower...