Incretins and their analogues as new antidiabetic drugs.

Glucagon-like peptide 1 (GLP-1) is a gut (incretin) hormone with multiple actions that could potentially contribute to an antidiabetic effect. This includes: (a) glucose-dependent insulinotropic actions; (b) glucagonostatic actions; (c) a reduction in appetite/promotion of satiety leading to reduced food intake and weight reduction; (d) the deceleration of gastric emptying; and (e) the stimulation of islet growth, differentiation and regeneration. Thus, multiple aspects of the type 2 diabetic phenotype can potentially be improved or even corrected by GLP-1. The native gut hormone, however, after intravenous injection or absorption from subcutaneous depots, is proteolytically degraded and eliminated from the circulation too quickly to be useful for the treatment of diabetes. GLP-1 derivatives (receptor agonists) with prolonged pharmacokinetics that promise a potential for clinical use in the near future are being developed.