Glucagon-like peptide-1: physiology and therapeutic potential

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Abstract
Purpose of review Glucagon-like peptide-1 is a gastrointestinal hormone with a great diversity of actions. It is an established incretin hormone (intestinal enhancer of insulin secretion), although physiologically its most important actions may be to regulate nutrient entry, digestion, and deposition by actions on appetite, digestive functions, and the endocrine pancreas. However, recent studies have also implicated glucagon-like peptide-1 in the regulation of cardiovascular function and have suggested that glucagon-like peptide-1 may have neuroprotective effects. As a result of these actions, attempts are currently being made to convert glucagon-like peptide-1 into a clinically useful therapeutic agent for the treatment of type 2 diabetes. Native glucagon-like peptide-1 is not useful because it is inactivated in the body by the ubiquitous enzyme dipeptidyl peptidase IV. The strategies used, therefore, include development of inhibitors of dipeptidyl peptidase IV as well as resistant analogs of glucagon-like peptide-1. Recent findings Several inhibitors and analogs are currently undergoing extensive clinical investigation, and representatives for both have shown remarkable clinical efficacy in studies involving up to 52 weeks of administration, with sustained improvement in metabolic control and few and mild side effects. Although the analogs require injection, the inhibitors are orally available. On the other hand, the analogs, but not the inhibitors, consistently reduce body weight. Summary The principle of a glucagon-like peptide-1-based therapy of type 2 diabetes, therefore, currently appears most promising.