Review Article
Exenatide: A Novel Approach for Treatment of Type 2 Diabetes
Abstract
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.
Key Points
* Exenatide (synthetic exendin-4) is the agonist of GLP-1, the main incretin, i.e. an intestinal hormone that enhances glucose-induced insulin secretion.
* The antidiabetic effects of exenatide include stimulation of insulin synthesis and secretion, inhibition of glucagon secretion, delaying gastric emptying and possibly promotion of early satiety.
* The advantages of exenatide include moderate HbA1c reduction (approximately 0.8%) and slight weight loss (approximately 2 kg), but the drug is associated with increased frequency of nausea and has to be administered by subcutaneous injections twice daily.
* Exenatide may be a useful add-on therapy to obese patients with uncontrolled diabetes and/or postprandial hyperglycemia.
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