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The first antidiabetic treatment (exenatide; Byetta) based on the incretin hormone glucagon-like peptide-1 (GLP-1) was approved in 2005 as an adjunctive therapy in diabetic patients in whom sulfonylurea, metformin or both had failed. Many GLP-1 mimetics or dipeptidyl peptidase IV inhibitors are currently in clinical development for the treatment of type 2 diabetes and show promising results in the improvement of glucose homeostasis. Furthermore, the ability of GLP-1 to enhance pancreatic β-cell mass could delay progression of the disease. However, only several years of treatment in humans will confirm the long-term efficacy of GLP-1 mimetics and enhancers on glycemic control. To take advantage of the multifaceted actions of GLP-1, a better understanding of the physiological roles of GLP-1 is required.