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.
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
Catherine L
CL
Martin
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