Modifications to Glucagon-like peptide-1 (GLP-1) for type 2 diabetes and weight loss treatments

What is it about?

Glucagon-like peptide-1-based therapies are used to treat type 2 diabetes and for weight loss. However, as peptides, these molecules are subject to proteolytic degradation, and due to their low molecular weight they are renally filtered. Thus, GLP-1 exhibits a short circulation time. Attempts to improve the circulation time of GLP-1 have included alterations to its sequence, formulations, and conjugations to large carriers. Such approaches have led to GLP-1-based therapeutics that require once weekly (or longer) administration by injection.

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Why is it important?

GLP-1-based therapies are unlikely to cause low blood glucose, and cause no weight gain, or weight loss, and thus are of benefit for the treatment of type 2 diabetes. However, the cost of these therapies and their need in many cases for at least daily injection makes them inconvenient for patients. Making new drugs that act on the GLP-1 receptor, which cost less, do not require injection (i.e. can preferentially be taken via the oral route) or which can be administered less often (e.g. monthly) would greatly increase the utility of GLP-1-based therapies.

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