Exenatide Acetate has not been studied in patients with severe gastrointestinal disorders, including gastroparesis. Exenatide Acetate use is commonly associated with gastrointestinal adverse events, including nausea, vomiting, and diarrhea. 1 Exenatide is not recommended in patients with severe gastrointestinal disease.
Exenatide rarely reports deterioration of renal function (e.g., elevated serum creatinine concentration, impairment of renal function, worsening of chronic renal failure, and sometimes requiring hemodialysis in acute renal failure). Some of these events occurred in patients with nausea, vomiting and/or diarrhea with or without dehydration or in patients who received exenatide in combination with other drugs known to affect renal function (e.g., angiotensin converting enzyme inhibitors, non-steroidal anti-inflammatory drugs, diuretics). Exenatide has not been found to have direct nephrotoxicity in preclinical or clinical studies. Renal effects are usually reversible with supportive therapy and discontinuation of potentially pathogenic drugs, including exenatide.
In clinical trials, at least 5% of patients who received exenatide reported adverse reactions including nausea, hypoglycemia, vomiting, diarrhea, nervousness, dizziness, headache and indigestion.
Byetta should not be used in patients with severe renal insufficiency (creatinine clearance 30 mL/min) or end-stage renal disease and should be used with caution in kidney transplant patients. In patients with end-stage renal disease on dialysis, a single dose of Byetta 5 ug is poorly tolerated due to gastrointestinal side effects. Because Byetta may cause nausea and vomiting with transient hypovolemia, treatment may worsen kidney function. Caution should be used when initiating or increasing the dose of Byetta from 5 ug to 10 MCG in patients with moderate renal insufficiency (creatinine clearance of 30 to 50 mL/min).
Safety and efficacy have not been established in children under 17 years of age.
Incretin, such as glucagon-like peptide-1 (GLP-1), enhances glucose-dependent insulin secretion and exhibits other anti-hyperglycemic effects after their release from the gut into circulation. Byetta is a GLP-1 receptor agonist that enhances glucose-dependent insulin secretion in pancreatic beta cells, inhibits inappropriately elevated glucagon secretion, and slows gastric empties. The amino acid sequence of exenatide overlaps with that of human GLP-1. Exenatide has been shown to bind and activate the human GLP-1 receptor in vitro. This leads to glucose-dependent synthesis of insulin and increased insulin secretion in pancreatic beta cells through mechanisms involving cyclic AMP and/or other intracellular signaling pathways. Exenatide stimulates the release of insulin by pancreatic beta cells in the presence of elevated glucose concentrations.
