[Exenatide--an incretin-mimetic agent for the treatment of type 2 diabetes mellitus].
The incretin hormone glucagon-like peptide 1 (GLP-1) is being synthesized from L-cells in the gut and enhances glucose-induced insulin secretion. Metabolic control of type 2 diabetic patients can be markedly improved by additional administration of GLP-1, however, this peptide is almost immediately degraded and therefore has little clinical value. The synthetic GLP-1 agonist exenatide underlies a different metabolism and has recently been approved by the U.S. Food and Drug Administration for the adjunctive treatment of patients with type 2 diabetes who are suboptimally controlled with metformin and/or sulfonylurea. First controlled clinical trials provided evidence that glycaemic control under exenatide administered twice daily in a dose of 5-10 microg was not inferior to conventional insulin therapy. Novel aspects in the treatment of type 2 diabetes by GLP-1 receptor stimulation further include its influence on the insulin secretory pattern, insulin/glucagon ratio, body weight and possibly even pancreatic beta cell mass. However, a general application of exenatide in the treatment of type 2 diabetes will also largely depend on the therapy behavior of patients, a possible immunogenicity and the rate of adverse events. Furthermore, a possible indication for exenatide as first-line therapy of type 2 diabetes and the prognostic relevance of this novel therapeutic approach have yet to be defined.
Reuter
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Klinik III für Innere Medizin, Universität zu Köln, Köln. Hannes.Reuter@koeln.de
Erdmann
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D000595:Amino Acid Sequence; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D000077270:Exenatide; D005746:Gastric Emptying / Q000187:drug effects; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D052216:Glucagon-Like Peptide 1 / Q000737:chemistry / Q000502:physiology*; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007328:Insulin / Q000031:analogs & derivatives / Q000627:therapeutic use; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; D008687:Metformin / Q000627:therapeutic use; D010455:Peptides / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018027:Receptors, Glucagon / Q000819:agonists*; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D014688:Venoms / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*
C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D007328:Insulin; D049528:Insulin, Long-Acting; D010455:Peptides; D018027:Receptors, Glucagon; D013453:Sulfonylurea Compounds; D014688:Venoms; D000069036:Insulin Glargine; D052216:Glucagon-Like Peptide 1; D008687:Metformin; D000077270:Exenatide