Exenatide: from the Gila monster to the pharmacy.
OBJECTIVE
To explain the incretin concept and review the pharmacology and clinical utility of exenatide (Byetta-Amylin; Lilly), a new agent for the treatment of patients with type 2 diabetes mellitus, and provide pharmacists with information necessary for counseling patients in the use of exenatide.


METHODS
Review articles, clinical trials, and data on file with the manufacturers.


METHODS
By the authors.


METHODS
By the authors.


RESULTS
Exenatide is a synthetic form of a protein found in the saliva of the Gila monster that mimics the action of glucagon-like peptide-1, an incretin important in glucose homeostasis and deficient in patients with diabetes mellitus. Three pivotal clinical trials of exenatide as an add-on therapy in patients with type 2 diabetes mellitus who were unable to achieve glycemic control with maximum doses of metformin, sulfonylurea, or these drugs in combination demonstrated significant reductions in glycosylated hemoglobin (A1C) levels following twice-daily self-injection of exenatide compared with placebo. Weight loss was observed in patients in conjunction with A1C improvement, which occurred without additional patient instruction, intentional caloric deficit, or exercise. Mild-to-moderate nausea was the most common adverse event with exenatide treatment, occurring at the beginning of therapy, lessening over time, and reduced by titration of the dose.


CONCLUSIONS
Exenatide offers a wide range of beneficial glucoregulatory effects, including enhancement of glucose-dependent insulin secretion, restoration of first-phase insulin response, suppression of inappropriately elevated glucagon secretion, slowing of gastric emptying, and reduction of food intake. These positive effects depend on the patient's understanding of the proper administration technique and timing, the need for continued adherence, and what to do if adverse effects occur, all elements that can be conveyed by pharmacists in their counseling and education of patients with type 2 diabetes mellitus.
Triplitt
Curtis
C
Department of Medicine, Division of Diabetes, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA. curtis.triplitt@uhs-sa.com
Chiquette
Elaine
E
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000502:physiology; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000096:biosynthesis; D008116:Lizards; D010353:Patient Education as Topic / Q000458:organization & administration; D010455:Peptides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D014688:Venoms / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
D000077270:Exenatide; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D010455:Peptides; D014688:Venoms