The Food & Drug Administration recently approved exenatide (Byetta, Eli Lilly/Amylin Pharmaceuticals) as adjunctive therapy to improve glycemic control in those with Type 2 diabetes who are taking metformin, a sulfonylurea, or a combination of both. Exenatide is a synthetic analog of a peptide found in the saliva of the Gila monster, a poisonous lizard. The drug is currently available in pharmacies.
Exenatide is the first in a new class of drugs called incretin mimetics to receive FDA approval. According to Steven Edelman, M.D., professor of medicine at the University of California at San Diego and the San Diego Veterans Affairs Medical Center, the drug exhibits many of the same effects as glucagon-like peptide 1 (GLP-1), an incretin hormone produced in the human digestive tract. Edelman explained that GLP-1 stimulates glucose-dependent insulin secretion from the pancreas; works in the satiety centers of the brain, leading to reduced food intake; and suppresses inappropriate postprandial elevations in glucagon. Those with Type 2 diabetes have reduced levels of GLP-1, said Edelman.
Stuart Haines, Pharm.D., professor and vice-chair for education in the department of pharmacy practice and science at the University of Maryland School of Pharmacy in Baltimore, said that exenatide targets two issues faced by patients with Type 2 diabetes. He said it suppresses the postpranial blood glucose "excursions" that are the main problem early in the course of the disease. In addition, exenatide appears to preserve beta-cell function in the pancreas over an extended period, which may slow the progression of diabetes.
Exenatide can be administered anytime within the 60-minute period before morning and evening meals, according to Amylin and Eli Lilly. The manufacturers strongly cautioned that the drug should not be administered after a meal. Amylin and Eli Lilly said also that oral medications dependent on threshold concentrations for efficacy, such as oral contraceptives and antimicrobials, should be taken at least an hour before exenatide is administered.
Edelman noted that patients taking exenatide with a sulfonylurea may wish to empirically decrease the dose of the oral agent to reduce the risk of hypoglycemia. The manufacturers said hypoglycemia was rarely observed in those taking exenatide with metformin alone in clinical trials.
Lilly and Amylin cautioned that exenatide should not be used with Type 1 diabetes. The manufacturers also said that exenatide has not been studied in those with severe gastrointestinal disease, including gastroparesis. Haines said that exenatide may exacerbate the bloating and nausea sometimes associated with gastroparesis because it slows gastric emptying. Haines noted that because exenatide is eliminated predominantly by glomerular filtration, it is not recommended for those with end-stage renal disease or severe renal impairment (creatinine clearance <30 mL/min).
Edelman and Haines noted that the most frequently reported adverse event associated with exenatide use in clinical trials was mild to moderate, dose-dependent nausea.
Pharmacists should tell patients they may experience nausea, said Cameron Lindsey, Pharm.D., an assistant professor of pharmacy practice at the University of Missouri- Kansas City School of Pharmacy. She also mentioned that pharmacists should make sure patients know how to administer their subcutaneous injections. In addition, pharmacists can teach patients to recognize the signs and symptoms of hypoglycemia, she said.
"I believe exenatide will have a huge impact on the lives of those with Type 2 diabetes," Edelman concluded. "A drug that helps patients improve blood glucose control and lose weight has never been seen before."