title: Incorporating incretin-based therapies into clinical practice: differences between glucagon-like Peptide 1 receptor agonists and dipeptidyl peptidase 4 inhibitors.
abstract: Type 2 diabetes mellitus (DM) is a prevalent disorder that affects children, adolescents, and adults worldwide. In addition to risks of microvascular disease, patients with type 2 DM often have multiple risk factors of macrovascular disease; for example, approximately 90% of patients with type 2 DM are overweight/obese. Type 2 DM is a complex disease that involves a variety of pathophysiologic abnormalities, including insulin resistance, increased hepatic glucose production, and abnormalities in the secretion of hormones, such as insulin, glucagon, amylin, and incretins. Incretins are gut-derived peptides with a variety of glucoregulatory functions. Incretin dysfunction can be treated with glucagon-like peptide 1 (GLP-1) receptor agonists (eg, exenatide and liraglutide) or inhibitors of dipeptidyl peptidase 4 (DPP-4) (eg, sitagliptin and saxagliptin), the enzyme that degrades GLP-1. The GLP-1 receptor agonists and DPP-4 inhibitors both elevate GLP-1 activity and substantially improve glycemic control. The GLP-1 receptor agonists are more effective in lowering blood glucose and result in substantial weight loss, whereas therapy with DPP-4 inhibitors lowers blood glucose levels to a lesser degree, and they are weight neutral. Treatment with GLP-1 receptor agonists has demonstrated durable glycemic control and improvement in multiple cardiovascular disease risk factors. In addition, unlike insulin or sulfonylureas, treatment with a GLP-1 receptor agonist or a DPP-4 inhibitor has not been associated with substantial hypoglycemia. These factors should be considered when selecting monotherapy or elements of combination therapy for patients with type 2 DM who are overweight/obese, for patients who have experienced hypoglycemia with other agents, and when achieving glycemic targets is difficult.
authors.affiliation: Division of Endocrinology, University of Texas, Southwestern Medical Center, Dallas, USA. davidsonmd@sbcglobal.net
authors.forename: Jaime A
authors.initials: JA
authors.lastname: Davidson
mesh_terms: D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002648:Child; D048909:Diabetes Complications / Q000517:prevention & control; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis* / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control; D007003:Hypoglycemia / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D054795:Incretins / Q000008:administration & dosage*; D008297:Male; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D054795:Incretins; D052216:Glucagon-Like Peptide 1