The approved indication for exenatide was expanded with the Food and Drug Administration's approval of the glucagon-like peptide-1 (GLP-1) receptor agonist as monotherapy, as an adjunct to diet and exercise in adults with type 2 diabetes, the manufacturer announced.
Previously, exenatide (marketed as Byetta by Amylin Pharmaceuticals Inc. and Eli Lilly & Co.) was approved for type 2 diabetes in combination with diet and exercise and with other diabetes medications.
Approval was based on a study of 232 type 2 diabetes patients who did not achieve adequate glycemic control on diet and exercise alone and were randomized to treatment with one of two exenatide doses or placebo. At 24 weeks, reductions in hemoglobin A1c levels from baseline were significantly greater among those on 5 mcg or 10 mcg of exenatide twice a day compared with those on placebo, according to the revised label.
Nausea, the most common side effect, affected 3% of those on the 5-mcg dose and 13% of those on the 10-mcg dose, according to Amylin's announcement.
In addition to the new indication, the FDA approved changes to the safety information in the exenatide label, including pancreatitis in the warnings and precautions section, which addresses a previous FDA alert, and more information about exenatide use in patients with renal impairment. There have been postmarketing reports of acute pancreatitis associated with exenatide, including cases of fatal and nonfatal hemorrhagic or necrotizing pancreatitis. The label also advises against use of exenatide in patients with severe renal impairment or end-stage renal disease and recommends that it should be used cautiously in patients who have had a kidney transplant.
Exenatide, like other GLP-1 receptors, “enhances glucose-dependent insulin secretion by the pancreatic beta-cell, suppresses inappropriately elevated glucagon secretion, and slows gastric emptying,” according to the label. Exenatide should be injected subcutaneously within 60 minutes before morning and evening meals, or before the two main meals of the day, about 6 hours or more apart. The recommended starting dose is 5 mcg twice a day, increasing to 10 mcg twice a day after 1 month, depending on the patient's response.
The updated safety changes in the label are explained in a “Dear Health Care Professional” letter, which can be viewed at www.byettahcp.com/hcp/pdf/Dear%20HCP%20Letter.pdf