Exenatide: a novel approach for treatment of type 2 diabetes.
Exenatide (synthetic exendin-4) is the analog of glucagon-like peptide 1 (GLP-1), the major physiologic incretin. The latter is an intestinal hormone that enhances glucose-induced insulin secretion after meals. In addition, GLP-1 stimulates insulin synthesis, inhibits glucagon secretion, delays gastric emptying, and may promote satiety. These glucoregulatory actions help control plasma glucose in the postprandial period. However, in diabetes, the GLP-1 response to nutrient intake is impaired, leading to exacerbation of postprandial hyperglycemia. Exenatide was recently approved as adjunctive therapy in diabetic patients failing sulfonylureas and/or metformin. In clinical trials lasting 30 weeks, exenatide therapy was associated with moderate reduction in mean hemoglobin A1c (HbA1c) levels of approximately 0.8%, and an average weight loss of approximately 2 kg compared with baseline. Hypoglycemia was generally mild and occurred more commonly when exenatide was used in conjunction with sulfonylureas. The requirement of subcutaneous injections twice a day, and the frequent occurrence of nausea and vomiting, represent the main limitations of exenatide. Nevertheless, this agent may be a useful add-on therapy in obese diabetic patients with suboptimal control as a result of continuing weight gain and/or severe postprandial hyperglycemia. The introduction of GLP-1-based antidiabetic drugs is a novel and promising strategy to treat diabetes.
Mikhail
Nasser
N
Endocrinology Division, Olive View-UCLA Medical Center, 14445 Olive View Drive, Sylmar, CA 91342, USA. nmikhail@ladhs.org
D000218:Adamantane / Q000031:analogs & derivatives / Q000627:therapeutic use; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D000077270:Exenatide; D005746:Gastric Emptying / Q000187:drug effects; D005749:Gastric Inhibitory Polypeptide / Q000502:physiology; D005934:Glucagon / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000096:biosynthesis; D009570:Nitriles; D010455:Peptides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011759:Pyrrolidines; D016896:Treatment Outcome; D014688:Venoms / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000077597:Vildagliptin
D007004:Hypoglycemic Agents; D007328:Insulin; D009570:Nitriles; D010455:Peptides; D011759:Pyrrolidines; D014688:Venoms; D005749:Gastric Inhibitory Polypeptide; D005934:Glucagon; D000077270:Exenatide; D000077597:Vildagliptin; D000218:Adamantane