Incretin-based Therapies: Achieving Better Glycemic Control in Type 2 Diabetes

Wednesday, August 10, 2005

Corporate-sponsored Symposium

Supported by an educational grant from the Amylin-Lilly alliance

Faculty
John B Buse, MD, PhD
Daniel J Drucker, MD
Linda Siminerio, PhD, RN, CDE

Reported by Joelle Escoffery, PhD

This corporate-sponsored symposium addressed the clinical benefits of incretin mimetics, a new therapeutic option for the treatment of type 2 diabetes. The incidence of type 2 diabetes is continuing to increase, and current treatment options are limited by numerous side effects (eg, weight and hypoglycemia). Additionally, the efficacy of many current treatments declines over time, possibly due to the progressive decline of β-cell function associated with type 2 diabetes. Thus, treatments like incretin mimetics that have the potential to affect β-cell function are an important addition to the treatment paradigm for type 2 diabetes.

Incretin hormones are released from the gut in response to food ingestion. The incretin hormone glucagon-like peptide-1 (GLP-1) has been shown to stimulate glucose-dependent insulin secretion, suppress glucagon secretion, delay gastric emptying, promote satiety and weight loss, and may affect β-cell function. Among people with type 2 diabetes, GLP-1 secretion is decreased, but sensitivity to its actions is preserved, making GLP-1 receptor agonists an attractive therapeutic option.

Exenatide is an incretin mimetic that has been approved for use among people with type 2 diabetes who have failed treatment with metformin, a sulfonylurea, or metformin/sulfonylurea combination therapy. In clinical research, exenatide has been shown to improve insulin secretion and reduce body weight in these 3 patient groups. The most frequently reported side effects were nausea and hypoglycemia (primarily with sulfonylurea use). In terms of clinical use, exenatide is given as a twice daily injection, available in a pen device that delivers a fixed dose of either 5 μg or 10 μg doses. Treatment is usually initiated at a dose of 5 μg and titrated up to 10 μg after 1 month in order to reduce the incidence of nausea. It should be administered up to an hour before the morning and evening meal, and needs to be refrigerated.

When oral therapies are no longer effective, the next step in the treatment paradigm is to either initiate insulin injections or to initiate exenatide injections. When advancing patients to injectable therapies like insulin or exenatide, there are a number of barriers that both patients and healthcare providers face. Side effects, fear of needles, adherence issues, attitudes toward injections, and resource issues are all concern. Some issues, such as fear of needles and attitudes toward injections, are the same for all types of injections. Other issues, such as side effects, are different between the 2 treatments. Insulin is associated with weight gain and hypoglycemia, whereas the primary side effect for exenatide is nausea. Insulin also requires dose adjustment, whereas exenatide is administered as a fixed dose.