Management of type 2 diabetes: the role of incretin mimetics

Current strategies for the treatment of type 2 diabetes target deficient insulin secretion and insulin resistance, but have not been shown to correct the progressive β–cell dysfunction characteristic of the disease. Traditionally, type 2 diabetes is treated in a stepwise manner with medical nutrition therapy, oral anti–diabetes therapies, and ultimately exogenous insulin. These therapies improve glycemic control, but are unable to prevent or delay either deterioration in glucose control or the decline of β–cell function. Despite the use of current anti–diabetes therapies, patients with type 2 diabetes are likely to experience deteriorating glycemic control and substantial weight gain. In addition to these issues, patients treated with insulin secretogogues such as sulfonylureas and exogenous insulin are subject to an increased risk of hypoglycemia. Moreover, insulin–based therapies do not fully address the complex hormonal irregularities, such as glucagon hypersecretion, that characterize type 2 diabetes. In view of the drawbacks associated with current treatment strategies, new therapies are being developed that may provide more durable glycemic control with associated reductions in body weight. These new therapies include the incretin mimetics, agents that share many of the glucoregulatory effects of the incretin hormones such as glucagon–like peptide–1 (GLP–1). Leveraging the physiological functions of incretin hormones such as GLP–1 may potentially benefit the ever growing number of patients with type 2 diabetes. Drug Dev. Res. 67:545–552, 2006. © 2006 Wiley‐Liss, Inc.