Oral antidiabetic agents in type 2 diabetes

Abstract

Background: Oral antidiabetic agents differ with regard to mechanisms of action, hemoglobin A(1c)-lowering efficacy, safety, and tolerability. Traditional agents consist of those that enhance insulin secretion (i.e., sulfonylureas and glinides), those that enhance insulin sensitivity (i.e., metformin and the thiazolidinediones), and those that inhibit intestinal carbohydrate absorption (i.e., the alpha-glucosidase inhibitors). New oral agents include the dipeptidyl peptidase-4 (DPP-4) inhibitors, which potentiate the activity of the incretin glucagon-like peptide 1 and enhance glucose-dependent insulin secretion.

Scope: We review the characteristics of the traditional oral agents and these newer additions to the pharmaceutical armamentarium. Abstracts and original clinical and preclinical reports in the English language were identified for review based on MEDLINE literature searches (1970-2006) and abstract collections from major diabetes meetings.

Conclusions: Traditional oral agents provide significant treatment benefits for diabetic patients, including reduction in risk of microvascular complications. However, most patients with type 2 diabetes do not achieve target glycemic levels with traditional therapies, and these agents are also associated with hypoglycemia, weight gain, and poor tolerability. Oral DPP-4 inhibitors offer the potential for significant improvement in glycemic control without hypoglycemia or weight gain, although long-term durability of glycemic control (>52 weeks) has not been established.