Beyond glycemic control: the effects of incretin hormones in type 2 diabetes.
The improved understanding of glucoregulatory hormones has driven the development of new pharmacologic agents to treat type 2 diabetes. One new class of antihyperglycemic medication is incretin mimetics (IMs). Incretin hormones potentiate insulin secretion following meal ingestion, a process that is impaired in patients with type 2 diabetes. GLP-1, a 30-amino acid peptide incretin hormone, is produced in the L cells of the ileum and colon. Studies have shown that a 6-week continuous GLP-1 infusion in patients with type 2 diabetes improved glycemic control and beta-cell function and delayed gastric emptying. Despite the rapid degradation and inactivation of GLP-1 by the enzyme dipeptidyl peptidase IV (DPP-IV), agents that mimic the actions of GLP-1 are of great clinical interest. First-in-class IM exenatide, a GLP-1 receptor agonist resistant to DPP-IV inactivation, mimics many beneficial glucoregulatory effects of GLP-1, such as suppressing glucagon secretion, regulating gastric emptying and satiety, and increasing glucose-dependent insulin secretion. Exenatide is an adjunctive therapy for patients who take metformin, a sulfonylurea, a thiazolidinedione, or a combination of these oral medications but have not achieved glycemic control. An 82-week, open-label extension trial has shown that exenatide is well tolerated and that the benefits, including improved glycemic control, weight loss, and mitigation of cardiovascular risk factors, are sustained.
Martin
Catherine L
CL
Division of Metabolism, Endocrinology, and Diabetes, Michigan Diabetes Research and Training Center, University of Michigan Health System, Ann Arbor, MI 48109, USA. martinc@med.umich.edu
D002986:Clinical Trials as Topic; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000503:physiopathology*; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000493:pharmacokinetics / Q000502:physiology; D006207:Half-Life; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D054795:Incretins / Q000502:physiology* / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D010455:Peptides / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000627:therapeutic use; D014688:Venoms / Q000627:therapeutic use
D007004:Hypoglycemic Agents; D054795:Incretins; D007328:Insulin; D010455:Peptides; D045162:Thiazolidinediones; D014688:Venoms; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide