Dulaglutide

Dulaglutide is described in research literature as an IgG4-Fc fusion protein composed of two GLP-1(7-37) analog peptides linked to a human IgG4 Fc region through a flexible 16–amino acid Gly-Ser linker. The Fc domain includes the S228P mutation, which stabilizes the structure and prevents antibody half-exchange. 

Its prolonged half-life is achieved through FcRn-mediated recycling in endothelial cells. Unlike small-molecule peptide agonists such as liraglutide and semaglutide, dulaglutide is structurally classified as an Fc-fusion biologic.

Dulaglutide works by binding to GLP-1 receptors on pancreatic beta cells, where it enhances glucose-dependent insulin secretion. Insulin is released only when blood glucose levels are elevated, helping reduce the risk of hypoglycemia. 

It also suppresses glucagon release from pancreatic alpha cells, which leads to decreased hepatic glucose production. In addition, dulaglutide slows gastric emptying to help reduce post-meal blood sugar spikes and activates central GLP-1 receptors in the hypothalamus.