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To present an evidence-based evaluation of the antidiabetic drug exenatide.


The English literature from 1965 to January 2006 was reviewed by using data sources from MEDLINE, endocrinology textbooks, and manual searching of cross-references from original articles and reviews.


Glucagon-like peptide-1 (GLP-1) is the major physiologic incretin, a gut-derived hormone that enhances glucose-induced insulin secretion. Moreover, GLP-1 inhibits glucagon secretion, delays gastric emptying, and may promote satiety, leading to reduction of postprandial glucose levels. Exenatide (AC-2993, synthetic exendin-4) is a GLP-1 analogue that was recently approved as adjunctive therapy in patients with diabetes in whom sulfonylureas, metformin, or both have failed. Exenatide is administered by subcutaneous injections twice daily. The use of exenatide has been associated with a mean reduction in hemoglobin A1c levels of ˜0.8% and a mean weight loss of ˜2 kg after 30 weeks of therapy in comparison with baseline. Treatment-related hypoglycemia was generally mild and occurred more commonly in association with the use of sulfonylureas. In 5% to 10% of patients, however, exenatide could not be tolerated, mainly because of nausea and vomiting.


Exenatide is a moderately effective antidiabetic agent. Mild degrees of weight loss and hypoglycemia are its main advantages, whereas the frequent occurrence of nausea and vomiting and the requirement of subcutaneous administration are its strongest limitations. Nevertheless, this new drug may be a useful add-on therapy in obese patients with diabetes who have suboptimal control of their disease as a result of continuing weight gain, severe postprandial hyperglycemia, or both.

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