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Incorporating incretin-based therapies into clinical practice: differences between glucagon-like Peptide 1 receptor agonists and dipeptidyl peptidase 4 inhibitors Davidson JAMayo Clin Proc 2010[Dec]; 85 (12 Suppl): S27-37Type 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.|Adolescent[MESH]|Adult[MESH]|Blood Glucose/analysis[MESH]|Child[MESH]|Diabetes Complications/prevention & control[MESH]|Diabetes Mellitus, Type 2/*diagnosis/*drug therapy[MESH]|Dipeptidyl-Peptidase IV Inhibitors/*administration & dosage[MESH]|Dose-Response Relationship, Drug[MESH]|Drug Administration Schedule[MESH]|Drug Therapy, Combination[MESH]|Female[MESH]|Follow-Up Studies[MESH]|Glucagon-Like Peptide 1/administration & dosage/*antagonists & inhibitors[MESH]|Humans[MESH]|Hyperglycemia/prevention & control[MESH]|Hypoglycemia/prevention & control[MESH]|Hypoglycemic Agents/administration & dosage[MESH]|Incretins/*administration & dosage[MESH]|Male[MESH]|Randomized Controlled Trials as Topic[MESH]|Risk Assessment[MESH]|Severity of Illness Index[MESH]|Treatment Outcome[MESH]|Young Adult[MESH] |
