Originally identified in Gila monster lizard (Heloderma suspectum), Exendin-4 is an incretin mimetic, an analog of glucagon-like-peptide-1 (GLP-1), it stimulates insulin secretion and modulates gastric emptying to slow the entry of ingested sugars into the bloodstream. Exendin-4 is resistant to cleavage by plasma DPP-IV unlike GLP-1. This gives it a longer half-life and duration of action than GLP-1, as well as greater potency in vivo. Exendin-4 increases insulin sensitivity and improves glucose tolerance and is currently used for the treatment of Type 2 diabetes mellitus in its synthetic form Exenatide.

Exendin-4 also promotes the production and proliferation of β-cells leading to regeneration of the pancreas. It is a ligand to the exendin receptor and increases pancreatic acinar cell cAMP levels. However, the GLP-1 analog was found to have a toxic effect by inducing hypotension due to relaxation of the cardiac smooth muscle.

This exendin-4 peptide is provided with an N-terminal cysteine residue for conjugation reactions.