Is the GLP-1 system a viable therapeutic target for weight reduction?

Abstract

Incretin hormones are intestinally derived peptides that are known to augment glucose-stimulated insulin secretion and suppress glucagon levels. Incretin mimetics are attractive adjunctive therapy for type 2 diabetes due to its efficacy on reducing hyperglycemia with a minimal risk of hypoglycemia. In contrast to most available hypoglycemia agents that cause weight gain, incretin mimetics are associated with moderate weight loss. In this review, we focused our discussion on the actions of glucagon-like peptide 1 (GLP-1) in the brain regulation of energy expenditure and food intake. Furthermore, we reviewed the data from preclinical and clinical studies in humans and discussed the actions of GLP-1, GLP-1 analogs, dipeptidyl pepidase 4 (DPP-4) inhibitors on body weight regulation as well as mechanism by which these effects may occur. The gastrointestinal side effects common to GLP-1 based therapeutics such as nausea hamper its wide spread use. Here, we discussed theoretical possibilities for maximizing weight loss and minimizing nausea with of incretin-based therapy.