The potential role of glucagon-like peptide 1 in diabetes

Abstract

The incretin hormone glucagon-like peptide 1 (GLP-1) has a promising potential for the treatment of type 2 diabetes due to its glucose-dependent insulinotropic and glucagonostatic properties. In addition, the peptide potently decelerates gastric emptying and inhibits appetite, thereby leading to reduced food intake. In animal studies, GLP-1 has been demonstrated to increase B-cell mass via inhibition of apoptosis and stimulation of B-cell replication and neogenesis. However, an in vivo half-life in the range of minutes limits the therapeutic use of the native peptide GLP-1. Different pharmacological approaches to overcome these problems are currently being evaluated. They include the continuous parenteral administration of the peptide via infusion pumps, the inhibition of its in vivo degradation and the generation or use of modified derivatives/analogs of GLP-1 displaying prolonged biological activity. The physiological effects of GLP-1 and its pharmacokinetic limitations will be reviewed here, and the current therapeutic approaches based on GLP-1 discussed.