Therapies for Diabetes: Pramlintide and Exenatide

The American Diabetes Association currently recommends an A1C goal of less than 7 percent. However, many patients are unable to achieve this goal by using oral drug combinations or diet and exercise, leaving insulin as the only treatment option.

In most cases, insulin is initiated later in therapy because of its inconvenience and adverse effects (e.g., weight gain, hypoglycemia, possible role in atherogenesis). Although insulin effectively helps patients attain glucose goals, the search for new agents continues. Two injectable agents, pramlintide and exenatide, were approved in 2005 for the treatment of diabetes.

Pramlintide, indicated for use in patients with type 1 and 2 diabetes, is a synthetic analogue of human amylin that acts in conjunction with insulin to delay gastric emptying and inhibit the release of glucagon. Exenatide, a glucagon-like peptide-1 mimetic, has multiple mechanisms for lowering glucose levels, including the enhancement of insulin secretion, and is indicated for use in patients with type 2 diabetes.

Clinical trials have shown that both agents reduce, by a statistically significant degree, A1C levels (0.3 to 0.7 percent more than placebo), fasting plasma glucose levels, and body weight (3 to 5 lb [1.4 to 2.3 kg]). No studies have examined their effects on diabetic complications, cardiovascular disease, or overall mortality. Pramlintide and exenatide may help make glycemic goals more attainable.

Issues with Insulin Therapy

The 2006 American Diabetes Association (ADA) guideline recommends a general A1C goal of less than 7 percent; a higher goal may be appropriate in young children, older patients, patients with comorbid conditions, or patients in whom hypoglycemia poses a significant risk. Patients with type 2 diabetes are usually instructed on lifestyle modifications with or without oral therapy to manage the disease. In most patients, these treatment modalities eventually are not adequate to achieve glucose control because of declining beta cell function and increasing insulin resistance in the liver and muscle tissue. If blood sugar cannot be controlled with oral medications, insulin has been the alternative treatment. Insulin, however, is not favored by many patients and physicians because of the therapy's inconvenience, the need for frequent blood sugar monitoring, and the risk of weight gain and hypoglycemia.

Although studies have shown that insulin, used alone or in combination with oral agents, helps reduce A1C levels, the U.K. Prospective Diabetes Study found no significant reduction in macrovascular complications with intensive insulin therapy compared with sulfonylurea therapy or diet. The introduction of pramlintide and exenatide has given physicians additional treatment options to help improve glucose control.

MELISSA C. JONES, PharmD, BCPS, South University School of Pharmacy, Savannah, Georgia