Test Your Knowledge Answer #407

This patient has both fasting and postprandial hyperglycemia; however, her postprandial values are primarily responsible for increasing the hemoglobin A1C values. Of the answer options provided, the drug exenatide is most likely to reduce these levels. The United States Food and Drug Administration approved exenatide in 2005 for the treatment of type 2 diabetes. Exenatide is the synthetic version of the naturally occurring hormone exendin-4. Its mechanism of action is through the glucagon-like peptide-1 receptor. The effects of exenatide include simulation of glucose-dependent insulin secretion, inhibition of glucagon secretion, inhibition of hepatic glucose production, delayed gastric emptying, and appetite suppression. Exenatide has been associated with weight loss, especially when used in combination with metformin. Taken with breakfast and supper in fixed dosages of either 5 or 10 µg by injection with a pen device, exenatide has been shown to lower the hemoglobin A1C value by up to 1 percentage point when used in combination with a sulfonylurea, metformin, or both. Because exenatide stimulates insulin secretion in a glucose-dependent manner, there is no risk of hypoglycemia when this medication is used alone. When used in combination with a sulfonylurea, however, the risk of hypoglycemia is increased, so the dosage of sulfonylurea must be reduced.

 

• Understand that titrating oral agents beyond the maximal effective dosage will not affect glycemic control.
• The injectable drug exenatide is an option for patients with type 2 diabetes whose A1C values are above target owing to postprandial hyperglycemia.

Increasing glimepiride to 4 mg twice daily offers no benefit; sulfonylureas reach maximal therapeutic benefit at approximately half the maximum recommended dosage. Increasing metformin to 2550 mg daily offers little added benefit for similar reasons. Adding a thiazolidinedione may lower her hemoglobin A1C value an additional percentage point but may be associated with weight gain. Although not an answer option, intensive insulin therapy would also not be a successful intervention in a patient unwilling to transition from oral agents to insulin.